Electromagnetic Radiation and Human Health

EMF Protection

This ebook is the complete guide to learning about electrical sensitivity and how to prevent getting it in your life. You will learn what electrical sensitivity is, and what causes it. Once you have started learning about it you will learn how to get rid of it and protect yourself from the dangers of electrical sensitivity. You will also learn how to heal yourself. This book is the product of careful research by the scientific and medical communities into the dangers and preventative measures of electrical sensitivity. ES is one of the most under-diagnosed conditions in the world right now, and this ebook is designed to education people as to how it works and how to prevent it. Do not let it take hold of your family; take control and prevent it now! Do not let yourself get any more hurt; learn about this condition and fight it! Read more here...

How To Beat Electrical Sensitivity Summary

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Electromagnetic Fields

When the frequency increases, the electric and magnetic fields (EMF) cannot be separated from each other. If one of the fields exists, so does the other. They are linked to each other in every situation and this is described by Maxwell's equations 1 . The English scientist James Clerk Maxwell (1831-1879) presented the laws of electromagnetics without writing the equations as we know them today. With the existence of Maxwell's equations, EM wave propagation could be made possible. In addition, Maxwell brought together various laws of electrostatic and magnetic fields. While correlating them, he found that the result derived from Ampere's law was inconsistent in the time-varying field as it was based on stationary closed currents. To overcome this problem, Maxwell introduced a certain quantity called displacement current, which is proportional to the time derivative of D.

Electromagnetic Waves

The most important outcome of Maxwell's equations was the prediction of the existence of EM waves, which can be generated by oscillating electric charges. Maxwell proved that EM disturbances originated by one charged body would travel as a wave. Accordingly, Maxwell's equations can be combined to yield the wave equation that anticipates the existence of EM waves propagating with the velocity of light. Maxwell's equations are first-order equations. Eliminating one of the fields in these equations yields a second-order equation for the other field, which is called the wave equation or Helmholtz equation. Based on Maxwell's equations, around 1888, Hertz found, both theoretically and experimentally, that they included the notion of propagation of EM waves because of the specific coupling between the E and H due to the particular form of the vector equations 1 . For time-varying fields, E and H are coupled, but in the limit of unchanging fields they become independent. Practically, from...

International Commission on Nonionizing Radiation Protection

The ICNIRP's mission is to coordinate knowledge of protection against various nonionizing exposures in the development of internationally accepted recommendations. The ICNIRP guidelines 12-14 specify basic restrictions and reference levels. Basic restrictions on exposure to magnetic fields are based on established adverse health effects. For magnetic fields below 100 kHz, the physical quantity used to specify the basic restrictions is current density induced inside the body. Reference levels are values that are provided for practical exposure assessment purposes to determine whether the basic restrictions are likely to be exceeded. Compliance with the reference levels is designed to ensure compliance with the relevant basic restriction 14 .

Sources of Radiation Exposure

Lowest dose with notable bone marrow suppression with decrease in blood counts is 10 to 50 rem (100 to 500 mSv, 0.1 to 0.5 Gy). Lowest total body dose from ionizing radiation in which death may be seen is in the range of 1.0 to 2.0 Gy. Cause large doses of whole body radiation exposure.

To ionizing radiation

Power Doppler has been used to study the response of tumor blood vessels to ionizing radiation by utilizing amplitude to measure flow in microvasculature. For example, B16F0 melanoma, Lewis lung carcinoma (LLC), and GL261 glioma tumors were implanted in the hindlimb of C57BL6 mice, and D54 was implanted into nude mice. Tumors were grown to 1 cm in diameter and then irradiated with 2, 3, 6, or 10 Gy. Doppler analysis of tumor blood flow was performed on d 3 and 7. Figure 1 shows representative color Doppler images at d 3 of GL261 tumors treated with 0, 3, and 10 Gy. The flow in each pixel (power-weighted pixel) was accumulated to compare dose- and tumor-dependent changes in tumor blood flow over time. Figure 2 shows the dose-dependent tumor blood flow of all tumor models at d 3 after irradiation. Blood flow increased in all tumors receiving 2-3 Gy (Figs. 1B and 2), which is the fractionation scheme used during conventional radiotherapy. Doses used for stereotactic radiosurgery,...

Antiangiogenic agents enhance tumor control by ionizing radiation

Angiogenesis, the development of new blood vessels, is critical for human tumor growth. A single tumor blood vessel may feed as many as 10,000 tumor cells (49,50). Tumor blood vessel endothelium is derived from genetically stable host cell endothe-lium and is unlikely to acquire resistance to antineoplastic therapy (51). Antiangiogenic agents have been investigated as antineoplastic therapy in numerous preclinical trials. For example, antiintegrin alpha vs beta 3 inhibits breast cancer growth and angiogen-esis in human skin (52). Monoclonal antibody specific for vascular endothelial growth factor blocks human tumor growth in murine models (53). The addition of tetra-hydrocortisol, beta-cyclodextrin tetradecasulfate, and minocycline to standard cyto-toxic treatment suppresses LLC growth (54). TNP-470 alone or in association with minocycline represses murine FsaIIC fibrosarcoma and LLC growth in vivo when combined with cyclophosphamide (55). TNP-470 also enhances the antitumor effect of...

Electromagnetic Spectrum

According to the frequency, EM radiation is classified as either nonionizing or ionizing. Nonionizing radiation is a general term for that part of the EM spectrum with weak photon energy that cannot break atomic bonds in irradiated material, but still has a strong effect, which is heating. To understand this, consider the energy of a quantum of 50 Hz exposure, given by Planck's constant h times the frequency (50 Hz), which is 2 X 10-13 eV. As the energy required for ionization by breaking a chemical bond is typically 1 eV, it is clear that low-frequency fields do not cause ionization. Ionizing and nonionizing radiation are separated on the EM spectrum. The division between them is generally accepted to be at wavelengths around 1 nm in the far-UV region. Above that frequency is ionizing radiation, which contains enough energy to physically alter the atoms it strikes and change them into charged particles called ions. Below visible light is the nonionizing radiation. All types of EM...

Ionizing Radiation

The history of radiation carcinogenesis goes back a long way (reviewed in Reference 107). The harmful effects of X-rays were observed soon after their discovery in 1895 by W. K. Rontgen. The first observed effects were acute, such as reddening and blistering of the skin within hours or days after exposure. By 1902, it became apparent that cancer was one of the possible delayed effects of X-ray exposure. These cancers, which included leukemia, skin cancers, lymphomas, and brain tumors, were usually seen in radiologists only after long-term exposure before adequate safety measures were adopted, thus it was thought that there was a safe threshold for radiation exposure. The hypothesis that small doses of radiation might also April 26, 1986. A steam explosion blew the lid off the reactor. The graphite core caught fire and over 1019 becquerels (Bqs) of radioisotopes were released, producing a fallout that covered much of Belarus, Northern Ukraine, and part of the Russian Federation....

Radiation Exposure

ALLs occur less frequently following radiation exposure than do acute myeloid leukemias (AML), chronic myeloid leukemia (CML), or myelodysplastic syndromes. The incidence of ALL is modestly increased in populations exposed to ionizing radiation from an atomic bomb,26 39 and cases are most prevalent among younger survivors.40 As a general rule, most other forms of radiation may produce an excess of leukemia, again mostly of myeloid origin rather than lymphoid. No study has documented an increase in ALL associated with radiation from diagnostic radiographic pro-cedures.26

Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) has become a significant diagnostic procedure because of its high resolution. MRI is an imaging technique used primarily in medical settings to produce high-quality images of the inside of the human body. Today, MRI systems may subject the human body to fields between 3 and 4 T for a short period of time, although 1.5 T systems were the state of the art for clinical imaging two decades ago. MRI produces no ionizing radiation. It is believed to be harmless for humans as long as its magnetic field intensity is below the recommended safety limits.

Biological And Health Effects

EM fields and radiation can be envisaged as discrete quanta that are absorbed by matter. The amount of energy associated with a quantum is then decisive for the type of change that takes place initially. The quantum energies of EM waves are too low to break chemical bonds. However, there are structures in biological materials that may be affected by very low energy, e.g., hydrogen bonded structures in which very low energy may cause displacement of protons. The debate on the potential health effects of EM energy, especially from mobile phones, has focused on possible cancer-enhancing effects on one side, and influence on the CNS on the other side. It seems that any cancer-related effects of EM waves cannot be based on direct genotoxic effects, since the energy level is not high enough to damage DNA. Instead, it has been investigated whether EM fields are cocarcino-genic, i.e., whether they enhance the effects of other carcinogenic factors. Accordingly, it is important to know some of...

Brain and Nervous System

EM brain-mapping methods have been used extensively in the investigation of EM exposure. These methods, as compared to the brain imaging methods, are entirely passive and hence can be more easily applied to volunteers that is, there is no ionizing radiation and no strong magnetic fields. Interestingly, these methods have poorer spatial resolution than the imaging methods but superior temporal resolution (i.e., milliseconds (ms)). The main mapping technique used is EEG, which measures brain electrical activity. Depending on the number of channels used, sources of EEG signal can at best be estimated to within a few centimeters. State of the art EEG systems, now employing large numbers of electrodes ( 256 channels), have improved the spatial resolution of the cerebral cortex, but signals from deeper structures remain difficult to detect reliably 68 .

Maximum Permissible Exposure Values for Electric and Magnetic Fields

Many institutions and organizations throughout the world have recommended safety limits for EMF exposure. These include the Institute of Electrical and Electronic Engineers (IEEE) 5-8 , the National Radiological Protection Board (NRPB) of the United Kingdom 9-11 , the International Commission on Nonionizing Radiation Protection (ICNIRP) 12-14 , the Swedish Radiation Protection Institute 15 , Health Canada 16 , and the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) 17 . Table 3.1 shows various MPE values for EMF exposure 18-20 . A document by the International Commission for Electromagnetic Safety (ICES) (IEEE C95.6-2002) 25 that covers human exposure to EMF (0-3 kHz) has been released. Recommendations are given to prevent harmful effects in human beings exposed to ELF fields. The recommendations are intended to apply to exposures of the general public, as well as to individuals in controlled environments. They are not intended to apply to the purposeful exposure...

National Radiological Protection Board

The NRPB provides information and advice to officials in the United Kingdom responsible for the protection from radiation hazards either in the population as a whole or within population subgroups. The recommended NRPB guidelines 9-11 are the same for occupational and public environments. The basic restriction specified by the NRPB is an induced current density of 10 mA m2 in the head and trunk while the investigation levels for EMF exposure at 50 Hz are 12 kV m and 1600 T, respectively 26 .

Epidemiological Studies

The epidemiological studies correlate EMF exposure and health effects on human populations to establish quantitative dose-response relations. At best, the epidemiological findings indicate a correlation between EMF exposure and a health effect, but not necessarily a causal relation. Two major types of studies are used to evaluate whether an exposure is linked with a given disease the cohort and the case-control study designs. In a cohort study, exposed and unexposed populations are ascertained, then followed up to compare risks of developing particular disease outcomes. In an ideal case-control study, cases are those who have developed a particular disease in a specified population during the study period, and control subjects are a random sample of those in the population who have not developed disease 5,6 . Most epidemiological studies are limited by the use of surrogate indicators rather than direct measurements of exposure. An epidemiological...

Childhood Cancer and Leukemia

Leukemia is the most common cancer to affect children, accounting for approximately a third of all childhood cancers. As with most other cancers, the mechanism by which leukemia arises is likely to involve gene-environment interactions. Accordingly, it is important to identify exposures that cause DNA damage and induce chromosome breaks, which are inadequately repaired, ultimately leading to initiation and disease progression 9 . Childhood exposure to EMF has been studied intensively for many decades. However, research into this area gained momentum in 1979, when one of the first epidemiological studies 10 showed an association between exposure to EMF and cancer among children living near power lines. This study was followed by other studies of childhood cancer 11-20 . Although some studies have supported the findings of Wertheimer and Leeper 10 , more studies have failed to provide support for the hypothesis that EMF exposure increases the risk of childhood cancer. These studies...

Cardiovascular Diseases

Savitz et al. 53 investigated risk of cardiovascular disease in a cohort of 139,000 male utility workers. Exposure was assessed according to the duration of employment in occupations with exposure to magnetic fields. Overall mortalities due to cardiovascular disease were low. Sahl et al. 70 found that men working longer in high-exposure occupations or working as electricians, linemen, or power plant operators had no increased risk of dying from either acute myocardial infarction (AMI) or chronic coronary heart disease (CCHD) compared with men who never worked in high-exposure occupations. Their study was based on cohort of 35,391 male workers at the Southern California Edison Company between 1960 and 1992. In addition, another study of electrical utility workers 71 found no evidence that exposure to power-frequency fields was associated with heart disease.

Neurodegenerative Diseases

Ahlbom 74 conducted a systematic review of the literature on neurodegenerative diseases and exposure to EMF. The author concluded, For AD the combined data on an association with EMF are weaker than that for ALS. The association between suicide and EMF exposure was also weak. For depressive symptoms an assessment is more complex. For diseases such as Parkinson's, there is not enough information for an assessment. Overall, currently available data suggest a weak association between EMF exposure and noncancer health effects. More research, particularly from large epidemio-logical studies, is needed. An exception to the lack of association of miscarriages and exposure to 50-Hz magnetic fields are three studies 80-82 . They reported that high peak power-frequency exposures were associated with an increased risk of miscarriages in humans. The first population-based prospective cohort study 80 was conducted among pregnant women within a large health maintenance organization. All women with...

Cellular And Animal Studies

Laboratory studies provide another valuable source of information on the potential health risks of EMF. Laboratory studies on cells or on whole organisms play a key role in evaluating the response of different systems of the body. They lead to information about molecular mechanisms that can establish the scientific plausibility of effects under particular conditions. Laboratory studies are easier to control and provide the opportunity to check whether EMF exposure causes cancer or other illnesses, something that is not possible with human volunteers. However, laboratory studies entail complications of their own. For example, how should results obtained in only one animal be relevant or extrapolated to humans Cellular and animal experiments have enhanced our understanding of the health consequences of EMF exposure. They generally examine the effects of EMF exposure on cells and various systems of the body, in particular the immune, nervous, and endocrine systems. These systems are...

Genotoxicity and Carcinogenicity

The weight of any positive association between EMF exposure and cancer depends on the ability of exposure to interact with genetic material to damage it, therefore causing mutations, which may lead to cancer. There have been many studies that show EMF may affect DNA or induce mutations. Lai and Singh 100 at the University of Washington, Seattle, observed an increase in double-strand DNA breaks in brain cells of rats being exposed to a 60-Hz magnetic field at flux densities of 0.25 and 0.5 mT. In 2004, the same authors found an increase in DNA single-strand breaks after 2 h of exposure to magnetic field at intensities of 0.1-0.5 mT 101 . Wu et al. Other studies 105,106 suggested that environmental EMF exposures at 1-500 T flux densities are unlikely to cause DNA damage. However, the second study 106 did report that 7 mT caused DNA strand breaks when a strong oxidant was present. Williams et al. 107 reported that 14.6-mT ELF magnetic field exposure does not cause DNA breaks in...

Ornithine Decarboxylase ODC

ODC is an enzyme that plays an important role in regulating cell growth through synthesis of polyamines necessary for protein and DNA synthesis. It is an enzyme activated during carcinogenesis. Studies were carried out to investigate whether there were effects on ODC due to EMF exposure. An in vitro study 132,133 found increased ODC activity in three cell lines in response to a sinusoidal 60-Hz electric field (10 mV cm) for only 10 s duration. Stimulation in the activity of ODC in cultured cells by RFR with ELF modulation was also reported 134,135 . The results depended upon the type of modulation employed. These effects were noted only for certain modulations of the carrier wave, portraying the window effect (an effect that appears at certain frequency but not at higher or lower frequencies). In addition, changes in ODC have also been reported from EMF exposure in vivo 136 . It is clear from the literature that a variety of in vitro studies have demonstrated that EMF exposure affects...

Animal Cancer Studies

Animal studies presented mixed results but no direct carcinogenic effects have been observed. Future research may focus on the role of EMF as a tumor promoter or copromoter. Only a limited number of in vivo studies suggest a positive relationship between breast cancer in animals treated with carcinogens and magnetic-field exposure at approximately 0.02-0.1 mT. According to Loscher 150 , one area with some positive laboratory evidence of cancer incidence could involve animals treated with carcinogens during an extended period of tumor development.

Reproductive and Development

There is no strong evidence of reproductive or developmental effects of exposure to magnetic fields in experimental animals. Studies using mice and rats have shown that exposure to magnetic fields results skeletal malformations 160,161 , increase in placental resorptions 162 , and fertility 163 . However, Ryan et al. 164 studied the effect of magnetic field (2, 200, and 1000 T continuous exposure and 1000 T intermittent exposure) on fetal development and reproductive toxicity in the rodent. There was no evidence of any maternal or fetal toxicity or malformation. Elbetieha et al. 165 found that exposure of male and female mice to 50-Hz sinusoidal magnetic field (25 T) for 90 days before they were mated with unexposed counterparts had no adverse effects on fertility and reproduction in mice. Other studies also have reported no major effects on reproduction and development in mice 166-171 . Brent 172 reviewed in vivo animal studies and in vitro tests, as well as the biological...

Perception and Sensitivity

A syndrome called electrosensitivity or electromagnetic hypersensitivity (EHS) initially appeared in Norway in the early 1980s among users of VDTs 178 . The syndrome has included various nonspecific health symptoms such as skin reaction, elec-trophysiological changes in the CNS, respiratory, cardiovascular, and digestive effects. Mueller et al. 179 reported that some people appear able to detect weak (100 V m and 6 iT) EMF, but the ability to detect the fields is unrelated to whether the person is electrosensitive. 60 years. Electrosensibility was investigated and characterized by perception threshold and its standard deviation (SD). By analyzing the probability distributions of the perception threshold of electric 50 Hz currents, evidence could be found for the existence of a subgroup of people with significantly increased hypersensibility who as a group could be differentiated from the general population. The presented data show that the variation of the electrosensibility among the...

Cardiovascular System

In a recent review of the literature involving the effects of magnetic fields on microcirculation and microvasculature, McKay et al. 198 indicates that nearly half of the cited experiments (10 of 27 studies) report either a vasodilatory effect due to magnetic field exposure, increased blood flow, or increased blood pressure. Conversely, three of the 27 studies report a decrease in blood perfusion pressure. Four studies report no effect. The remaining 10 studies found that magnetic field exposure could trigger either vasodilation or vasoconstriction depending on the initial tone of the vessel.

Riadh W Y Habash

BIOEFFECTS AND THERAPEUTIC APPLICATIONS OF ELECTROMAGNETIC ENERGY BIOEFFECTS AND THERAPEUTIC APPLICATIONS OF ELECTROMAGNETIC ENERGY Bioeffects and therapeutic applications of electromagnetic energy author, Riadh Habash. p. cm. 1. Electromagnetism--Physiological effect. 2. Electromagnetic fields--Health aspects. 3. Electromagnetic fields--Therapeutic use. I. Title. DNLM 1. Electromagnetic Fields. 2. Complementary Therapies. 3. Radiation Injuries prevention & control. 4. Radiation. QT 34 H113b 2008

Waveguides

Waveguides are found in several forms. They can have a circular or a rectangular cross section. They may have other shapes as well, if utilized and manufactured for specific applications. Waveguides normally consist of metallic hollow structures used to guide EM waves, as shown in Figure 1.14. They are used for transferring signals, where the wavelengths involved are so short that they are of the same size range (2 GHz and higher). Large waveguides would be required to transmit RF power at longer wavelengths. Waveguides are low loss, which means the wave travels along the waveguide without greatly attenuating as it goes. Waveguides can be

Antennas

The antenna is the last component in the wireless transmitting system. The antenna is a device that provides the transition from a guided EM wave on a transmission line to an EM wave propagating in free space. Also, the antenna may be considered as a transducer used in matching the transmission line or waveguide to the surrounding medium. Most antennas are reciprocal devices, which means the antenna performs equally well as either transmitting antenna or receiving antenna. The purpose of the transmitting antenna is to radiate EM waves into free space (usually, but not necessarily, air). Antennas are also used for reception to collect radiation from free space and deliver the energy contained in the propagating wave to a feeder and receiver.

Antenna Properties

Polarization The polarization of an EM wave is the orientation of the electric field intensity vector E relative to the surface of the Earth. The propagating wave has a transverse direction for the electric field called the polarization direction. This normally lies along the direction of the electric field. There are two basic types of polarization linear and elliptical. Linear polarization is divided into two classes, vertical and horizontal. Circular polarization is the more common form of elliptical polarization. Two classes of circular polarization exist, right-hand circular and left-hand circular. Far-field zone This is the region far enough from the antenna where the radiated power per unit area decreases with the square of the distance from the source. In the far-field environment, the EM field propagates away from the source of radiation. The radiated energy is stored alternately in the electric and magnetic field of the propagating EM wave. The electric field vector and the...

Cancer Mechanisms

Cancer is a term applied to describe at least 200 different diseases, all of which involve uncontrolled cell growth. Cancer is a case of uncontrolled mitosis in which cells randomly divide and grow after escaping the body's normal control condition. As a primary disorder of cellular growth and differentiation, cancer is essentially a genetic disorder at the cellular level. With cancer, the fault is in the cell itself rather than in the overall body. Causes of most cases of cancer are unknown, but factors that influence the risk of cancer are many. Each of the known risk factors such as smoking, alcohol, diet, ionizing radiation, or others contributes to specific types of cancer. Cancer risk is related to many causes. The risk with asbestos is related to fiber length and toughness. The risk from particles in air pollution is related to their size and propensity to settle in the lung. Ionizing radiation has sufficient energy to directly initiate cancer. Visible light breaks bonds in the...

Swedish Standards

Sweden has been a leader in developing recommended visual ergonomic and EM emission standards for computer displays. Two prominent measurement and emission guidelines for monitors have emerged during the past few years. One, known as MPR-II, prescribes limits on EMF emissions in the ELF and VLF ranges, as well as electrostatic fields. Many major manufacturers of computer displays have embraced the Swedish guidelines. Nevertheless, the Swedish Confederation of Professional Employees (TCO), which represents over a million workers, requested more restrictive limits and test protocols. TCO published its own series of guidelines TCO'90, TCO'92, TCO'95, and TCO'99, which in reality are a copy of MPR-II with some adjustments 15 . In addition, recent TCO guidelines include guidelines for energy consumption, screen flicker, luminance, and keyboard use.

Restrictions

Most of the above exposure guidelines are based on recognized and reproducible interactions between EMF and the human body. The observed effects were all acute effects of EMF exposure on excitable tissue, such as nerve and muscle. The basic restriction in all exposure guidelines has, to date, been specified in terms of induced current density as the principal measure of interaction of EMF with the body rather than the more directly relevant internal electric field. The use of current density originated for the pragmatic reason that data were more readily available in terms of current density than electric field. The data used in the early days to determine the thresholds for nerve and muscle tended to be investigated using injected currents, with the current density being calculated from the injected current on the basis of the geometry without requiring conductivity information 26 . Other investigators suggested the use of internal electric field as a basic restriction in future EMF...

Measurement Surveys

Engineering contributions in the field of EM risk have made it possible to assess the field strength or power density due to exposure from an EM source and check its compliance with exposure guidelines. Theoretical calculations are adequate in some situations but measurements often prove more conclusive and less expensive, particularly at multiple-source sites. Therefore, theoretical calculations, particularly computational methods, are often not enough to assess compliance with safety limits. For this reason, EM measurements are usually performed to assure compliance with relevant guidelines to prevent overexposure conditions that could pose short- and long-term health problems. Measurements are also needed when the calculated fields are close to the threshold for overexposure or when fields are likely to be distorted by reflection from various objects 1 . In addition, assessment of EMF exposure levels for the general public and those associated with particular occupations provides...

Site Surveys

Safety regulations stipulate field limits in occupational and public environments, and thus there is a need for field measurement surveys. Such surveys are usually performed for one or more of the following reasons (1) to evaluate a space where electrical devices are being greatly affected by electrical installation systems or other electromagnetic interference (EMI) sources, (2) to evaluate the impact of power lines or other electrical facilities and to provide guidance in the installation of further structures, (3) to assess the exposure conditions in homes or offices to assure compliance with relevant safety standards, and (4) to prevent overexposure conditions that may pose short- and long-term health problems. The instruments used to measure EMF are well developed, especially those designed to measure magnetic fields. Besides simple handheld survey meters, there are now portable personal meters that are able to record and illustrate the various characteristics of field exposure....

Public Environments

Public environments in which EMF exposures can occur include residences and schools, and transportation facilities. The primary sources of residential and school fields are power lines, distribution lines, substations, wiring, grounding systems, and various electrical appliances. Sources of fields in trains and cars are mainly from the power lines supplying energy to the trains. Li et al. 8 investigated whether the age at cancer diagnosis was associated with residential exposure to magnetic fields. They compared average ages at diagnosis for cases of leukemia, brain tumor, or female breast cancer with elevated exposure (magnetic flux density 0.2 T, or residential distance from major power lines 100 m) to average ages at diagnosis for cancer cases with same diagnoses but with a background exposure (100 m from major power lines). They noted an association between magnetic field exposure and a greater mean age at diagnosis for brain tumors. The difference was greater for males than for...

Melatonin Hypothesis

Circadian rhythms of pineal activity and melatonin release. The melatonin hypothesis, first proposed many years ago, explained how EMF exposure is related to certain kinds of hormone-dependent cancers, particularly breast cancer. Kato et al. 87 , Wilson et al. 88 , and Huuskonen et al. 89 reported that exposure to magnetic fields between 1 and 130 T caused a decrease in melatonin levels in rats and hamsters. However, other studies found no evidence of any effect on melatonin in baboons, rats, and mice at fields between 1 and 100 T 90-97 . Karasek and Lerchl 98 reported the results of 60 independent assessments in animals of EMF exposure and nocturnal melatonin. Fifty-four percent reported no effect or inconsistent effects, 43 reported decreased melatonin, and 3 reported increased melatonin. Juutilainen and Kumlin 99 reported that daytime occupational exposure to magnetic fields enhances the effects of nighttime light exposure on melatonin production. Juutilainen and Kumlin reanalyzed...

Cell Proliferation

Altered proliferation of cells in vitro due to EMF exposure has been observed in a number of studies 124-127 . However, Aldinucci et al. 121 investigated whether static fields at a flux density of 4.75 T, generated by an nuclear magnetic resonance (NMR) apparatus, could promote movements of Ca++, cell proliferation, and the eventual production of proinflammatory cytokines in human peripheral blood mono-nuclear cells (PBMC) as well as in Jurkat cells, after exposure to the field for 1 h.

Immune System

In most studies, EMF exposure appears to have no effect on the immune system. House et al. 137 exposed mice and rats to 2, 200, and 1000 T (60 Hz) continuously. No significant change in the distribution of lymphocyte subsets in the spleens of exposed mice was observed when compared with controls. They concluded that exposure of mice to linearly polarized, sinusoidal 60-Hz magnetic fields at strengths up to 1000 T for up to 3 months did not significantly affect a broad range of immune effect or functions. In a study of human white blood cells, Aldinucci et al. 120 found no effect of a 4275-mT field on the inflammatory response of normal or leukemic cells. Onodera et al. 138 reported that exposure of immune system cells to 1-T field caused the loss of some cell types if the cells had been stimulated to divide, but

Behavioral Effects

There is insufficient evidence that EMF exposure at environmental levels causes behavioral changes of animals. Coelho et al. 151 reported that exposure to electric fields at 30 kV m (60 Hz) increased the occurrence of three out of ten categories of social behavior of baboons during a 6-week exposure, compared with equivalent rates observed in 6-week pre- and post-exposure periods. Trzeciak et al. 152 noted that exposure to magnetic fields (50 Hz, 18 mT) had no effect on open-field behavior of 10-12 adult male and female Wistar rats. But the investigators recommended the need for further studies to fully determine conditions under which an effect can be observed. Meanwhile, Sienkiewicz et al. 153 reported that short-term, repeated exposure to intense magnetic fields might affect the behavior of mice. Mice were exposed each day to a 50-Hz magnetic field before being tested in a radial arm maze, a standard behavioral test of the ability of mice to learn a procedure for seeking food....

Brain and Behavior

The CNS is a potential site of interaction with EMF because of the electrical sensitivity of the tissues. Lyskov et al. 181,182 performed spectral analysis of EEG recorded from volunteers exposed to a 45-Hz, 1.26-mT magnetic field. Significant increases in the mean frequency and spectral power were observed in the a and p bands of the spectrum. Although the evidence for an association between EMF exposure at levels lower than MPE values and brain activity is inconclusive, research on brain functions due to prolonged exposure should be investigated in future research.

Clinical Studies

Clinical studies carefully utilize screened volunteers who participate in double-blind studies, where appropriate, performed in a certified exposure facility. These studies investigate effects of EMF exposure on various senses, hormones, and organs, such as hearing, the brain, the cardiovascular system, the immune system, melatonin, and the eyes. EMF effects might be studied safely and effectively in the laboratory with human volunteers in spite of limitations to the duration of exposure and types of tests that are performed. The focus in human studies is usually on the effects that occur within a time frame of minutes, hours, days, or perhaps weeks. Longer-term studies with controlled exposure are difficult, if not impossible, to carry out with human volunteers in laboratory settings. The selection of physiological mechanisms for study is also limited to those that can be measured by noninvasive or minimally invasive procedures. Various health effects are claimed by people due to EMF...

Clinical Features Of Chronic Myeloid Leukemia

CML has an annual incidence of approximately 1.5 105, accounting for some 5000 new patients per year in the United States. Males are slightly more frequently affected than females (ratio 1.7 1), but there is no significant ethnic or geographical predisposition (1). The disease can occur at every age but the incidence greatly increases in the older population. Exposure to ionizing radiation is the only established risk factor, as demonstrated by the increased incidence in the survivors of the atomic bombs in Japan (2). Symptoms include weight loss, fever, and abdominal fullness but at least in the developed countries many patients are asymptomatic at diagnosis, when an abnormal routine blood count leads to a diagnostic work up.

Electricity Inside Us

For more than four centuries scientists have been attempting to define the role of electromagnetic phenomena in the life of humans and animals. But only after Hans Christian Oersted discovered that the electric current flowing through a wire loop can deflect a magnetized needle, did it become possible to create sufficiently sensitive galvanometers. With the help of these galvanometers, Carlo Matteuchi (1838), and later Emil du Bois-Reymond (1848), measured the electrical fields generated by the contraction of the muscles of animals and humans. However, living organisms are not only generators of electricity, but have high sensitivity to an electromagnetic field, whereby it is in no way possible to explain the observed effects by the thermal action of such a field. consciousness and of the sensitivity to pain) can be obtained by passing the impulses of alternating current through a human brain, which is frequently used for anesthesia during surgical procedures. The direction of the...

Radiosensitizing abilities of the taxanes

The taxanes act to cause cells to arrest their progression through the cell cycle at the G2-M phase. This is of significant interest because this is exactly the point in the cell cycle where cells are more sensitive to the lethal effects of ionizing radiation (37). Taxanes also act to induce programmed cell death. Milas et al. have looked at the relationship among mitotic arrest, apoptosis, and the antineoplastic activity of paclitaxel in 16 murine tumors (38). Using a single dose of paclitaxel of 40 mg kg, mitotic arrest was induced in all tumors in varying degrees, however, apoptosis was induced in only 50 of tumors. The antitumor efficacy of paclitaxel correlated best with mitotic arrest as quantitated by absolute growth delay. This study also showed that the pretreatment levels of apoptosis correlated with both paclitaxel-induced apoptosis and tumor growth delay. Therefore both pretreatment apoptotic rate and paclitaxel apoptotic rate could potentially act as predictors of the...

Double Strand Breaks

Double-strand breaks (DSBs) result from exposure to ionizing radiation, x-rays, from enzymatic cleavage, or during replication of a single-strand break. DSBs are especially problematic because of the absence of a normal strand to serve as a template. Arrest of the cell cycle to facilitate repair of the DSB is mediated by p53. DNA damage-response proteins, including ataxia-telangiectasia mutated (ATM) and ataxia-telangiectasia related (ATR), are recruited. There are two logically alternate pathways for double-strand break repair, homologous recombination or nonhomologous end joining, which are reviewed elsewhere (16,17).

Ongoing clinical experience

Although the systemic activity of gemcitabine has been examined in many tumor sites, the role of this drug in combined modality therapy remains undefined for a number of human tumors. The following is an overview of the current results of investigations involving gemcitabine in locally advanced tumors in combination with ionizing radiation.

Novel chemotherapeutic agents

Owing to the lack of any single sufficiently promising phase II experience for radio-surgery-ineligible GBM patients, recent RTOG studies have focused on testing new systemic agents with cranial radiation. A phase I study of topotecan plus cranial radiation for GBM patients was completed, in an effort to enhance antitumor response by exploiting the strand break mechanisms of both topotecan and ionizing radiation. Preliminary toxicity data were acceptable and a dose level of 1.5 mg m2 was chosen (50). Preliminary data from the phase II study 95-13 has been reviewed, and initial analysis has thus far not demonstrated a survival benefit. Malignant gliomas are generally highly vascular and angiogenic tumors and thus may be appropriate targets for angiogenesis inhibitors. Recent experimental evidence has shown that inhibition of angiogenesis leads to radiosensitization. A phase II trial (RTOG 98-06) has recently been completed using thalidomide, a basic fibroblast growth factor (bFGF)...

Oxygen Free Radicals Aging And Cancer

8-hydroxyadenine, and formamido derivatives of altered purines.119 Some of these products appear in the urine and may be an index of oxidative damage. They are also produced by exposure of DNA to ionizing radiation and oxygen-radical generators. 8-Hydroxyguanine appears to be the most frequently altered base to result from oxi-dative damage to DNA, and if this base is left unrepaired in DNA it produces G T trans-

Cell Cycle Responses to DNA Damage

Early studies with mammalian cells uncovered a delay in G2 that occurred within 2 h of exposure to ionizing radiation (reviewed in 53). This delay was found to be transient, with cells entering mitosis after a time that depends on the dose of ionizing radiation. A division delay in response to DNA damage was observed in diverse cell types, including amoeba, yeast, sea urchin eggs, and mammalian cervical cancer cells (53). Part of the basis for the division delay is that cells are blocked in G2 in response to DNA damage. The early method of determining the G2 delay was to count mitotic cells shortly after irradiation or adding DNA-damaging chemicals. G2 delay is characterized by a rapid reduction in the number of mitotic cells. Mitosis must be analyzed quickly to eliminate possible contributions of alternate points of arrest in the cell cycle. For example, if the reduction in mitotic cells occurs after 8 or 10 h (significantly longer than the G2 M period of approx 4-5 h) the blockage...

Biochemical Spectroscopy Overview

Spectroscopic methods are used in the structural characterization of biomolecules (Bell, 1981 Campbell and Dwek, 1984 Greve et al., 1999 Hammes, 2005). These methods are usually rapid and noninvasive, require small amount of samples, and can be adapted for analytical purposes. Spectroscopy is defined as the study of the interaction of electromagnetic radiation with matter, excluding chemical effects (photochemistry refers to the interaction with chemical effects). The electromagnetic spectrum covers a wide range of wavelengths (Figure 7.1). The interaction of electromagnetic radiation with matter gives rise to scattering, absorption or emission of the radiation. Scattering is usually detected by measuring the intensity of radiation at some angle 0 to the incident wave (turbidity refers to measuring the reduced transmitted light at 0 0). Electrons are the usual scatterers in molecules, while nuclei scatter neutrons. If the scattered radiation has the same frequency as the incident...

The Molecular Basis of G2 Arrest

A number of other Rad mutants that fail to arrest in the cell cycle in response to ionizing radiation have been uncovered, and orthologs in various organisms including mammals have been identified (reviewed in 5961). Studies on the components of the DNA-damage response have uncovered three main groups of proteins involved in initiating G2 arrest. The sensors recognize damaged DNA, and the transducers transmit the signal downstream to the effectors, whose activity is modulated to bring about arrest (61,62). Although these groups of proteins are sufficient to induce the arrest, in time, many checkpoints become spontaneously inactivated, and additional mechanisms are used to maintain the arrest. Studies with mammalian cells in tissue culture showed that Cdc2 is an important effector for the G2 checkpoint. Ionizing radiation and other forms of DNA damage blocked the dephosphorylation of Cdc2 at tyrosine 15 and threonine 14, causing it to remain inactive (63,64). Inhibition of...

Infrared Spectroscopy

The energy of most molecular vibrations corresponds to that of the IR region of the electromagnetic spectrum. Molecular vibrations may be detected and measured either in an IR spectrum or indirectly in a Raman spectrum. The common region of the IR spectrum is 2.5-16 i (4000-625 cm-1), which most IR spectrometers cover. Infrared light is absorbed when the oscillating dipole moment (due to a molecular vibration) interacts with the oscillating electric vector of the infrared beam. A simple rule for deciding if this interaction (and hence absorption of light) occurs is that the dipole moment at one extreme of a vibration must be different from the dipole moment at the other extreme of the vibration. Thus the selection rule for a vibration to be IR active is that the vibration must result in a change in the dipole moment. The important consequence of this selection rule is that in a molecule with a center of symmetry, those vibrations symmetrical about the center of symmetry are inactive...

Contribution of p53 to G2 Arrest

The first clue that p53 was important for DNA-damage responses was that the levels of p53 protein were elevated when cells were exposed to ultraviolet radiation (126). Proof for this idea was provided by the observation that p53 was required for the G1 arrest that occurred in response to ionizing radiation (127). Human cells lacking p53 bypass the G1 checkpoint, progress through S phase, and accumulate in G2, showing that G2 arrest still occurs in cells lacking p53 (127). However, we found that when p53 is overexpressed in the absence of any other stress, this could also arrest cells in G2 (128). These and other studies showed that p53-independent pathways are sufficient to induce G2 arrest, and that p53 is also involved, probably to ensure the long-term sta

Caveolin1 as a Targeted Therapy in Pancreatic Ductal Adenocarcinoma

Targeting strategies against central regulatory molecules involved in PDA tumori-genesis have the potential to improve cancer therapy and patient survival. Here are a few examples of pre-clinical experiments that underscore this point. Cordes et al. have demonstrated that human pancreatic cancer cells can be rendered sensitive to ionizing radiation therapy by means of Cav-1 knockdown in two-dimensional (2D) grown cell culture 39 . Hehlgans et al. recently showed that Cav-1 could be used as a potential target molecule in human PDA cells in a 3D cell culture model. In these studies, Cav-1 was overexpressed into MiaPaca2 and Panc1 PDA cell lines, which increased cell survival after treatment with radiation. In contrast, silencing of Cav-1 expression via siRNA oligonucleotides made cells more radiosensitive 40 . Based on this body of work, knowledge of the Cav-1 expression in a patient's resected tumor sample may prove useful as a predictive biomarker for their response to radiation...

Epidemiology and etiology

In spite of these clinical associations, the etiology of Ewing sarcoma continues to elude identification. There does not appear to be an association with familial cancer syndromes, and there are only rare case reports of Ewing sarcoma occurring in siblings 4951 . Unlike the situation with osteosarcoma, it is quite uncommon for Ewing sarcoma to occur as a secondary cancer following ionizing radiation and chemotherapy 52 . In one retrospective analysis of second tumors following radiation therapy it was noted that 3 of these tumors were Ewing sarcomas, while 69 of secondary tumors following radiation were osteo-sarcomas. No specific environmental factors have been identified as causal 5 .

Technologies in MHealth

Conventional wired communications use conductors (twistedpair copper wires or coaxial cables) or optical fibers to send and receive data, whereas wireless communications utilize electromagnetic waves without relying on wires. There are a number of interesting facts associated with electromagnetic waves. With equal power levels, waves with lower frequencies tend to travel farther than higher-frequency waves. And lower-frequency waves tend to penetrate objects better than higher-frequency waves. For example, FM radio

Frequent Inactivation Of Atm In Sporadic Leukemias

The latter possibility is supported by multiple studies that have found that cells from some, but not all, heterozygote members of AT families respond abnormally to DNA damage. These abnormalities are mild compared to those seen in AT patients, but include increased sensitivity to the cytotoxic and clastogenic effects of ionizing radiation and radiomimetic drugs, persistence of radiation-induced chromosome breaks, postirradiation DNA synthesis abnormalities, and prolonged G2 arrest (reviewed in Ref. 3). ATM heterozygotes also are more likely than normal individuals to suffer from late in vivo side effects of radiation therapy (267,268). Data from Atm+' mice support the conclusion that individuals with one functional ATM allele have impaired responses to DSBs. Fibroblasts and lymphocytes from Atm+' mice have cell cycle checkpoint abnormalities and are sensitive to the killing effects of ionizing radiation (100,269), Atm+' mouse embryonic fibroblasts (MEFs) are more readily transformed...

Lessons For Cancer Screening

ATM heterozygotes would appear to be a high-risk group that could benefit from mammographic screening. However, it has been suggested that physicians consider alternatives to mammography in ATM heterozygotes (214,279). This issue has provoked much discussion, both pro and con (e.g., see Refs. 280-284). Typical radiation exposures to the breasts from mammography average 2-3 mGy AT patients respond poorly to treatment regimens that include ionizing radiation, radiomimetic drugs, and topoisomerase inhibitors. Care must be taken to modify standard protocols so as to minimize iatrogenic damage, but reduced therapeutic regimens can be tolerated for these individuals (e.g., see Refs. 15, 36, and 290). ATM heterozygotes could, in theory, represent a significant fraction of cancer patients who have adverse responses to radiation and chemotherapy. Experimental evidence for this possibility is mixed (reviewed in Ref. 3). Many studies have demonstrated a group correlation between in vitro...

Isolation of new genetic biomarkers and elucidation of molecular mechanisms an inductive approach

Although gene arrays are a relatively new innovation, there are already several good examples in the scientific literature of the use of this technology in biomarker identification and interrogation of molecular mechanisms underlying a toxic event. One such publication is by Voehringer et al. 6 on an analysis of the molecular determinants of sensitivity to apoptosis of mouse lymphoma cells. A pair of lymphoma cell lines, one resistant to radiation-induced apoptosis and the other sensitive, were analysed by transcript profiling both before and after radiation exposure. The expression levels of some 11000 genes were monitored using an oligonucleotide-based array, and, unsurprisingly, a large number of

Using MR Technology What Are We Learning

All of us who were the first subjects for MR studies of course wondered if something in our bodies might dislike having our hydrogen protons subjected to such military discipline, but by now millions and millions of people have been scanned, and no adverse effects have been found. Unlike all other imaging procedures, this one requires no exposure to ionizing radiation and can therefore be used safely in large samples of healthy people. The simple description of how MR works in the paragraph above does not do justice to all the ways that collecting MR signals can be tweaked to produce information. The use of MR to obtain measurements of function is described in more detail in the next section. However, the application of MR to study brain structure is a fascinating and steadily developing discipline in and of itself. fMR has many advantages over PET. While maintaining a PET center is expensive, and few medical centers have one, every medical center has an...

B NBS Cellular Phenotypes

The documented clinical radiosensitivity of patients with NBS is reflected by at least a two-fold increase in cellular hypersensitivity to ionizing radiation (IR) of primary and immortalized NBS cells (2,10). This hypersensitivity is also evident following exposure of NBS cells to bleomycin, streptonigrin, etoposide, camp-tothecin, and the cross-linking agent mitomycin C, but not to ultraviolet wavelength C (UV-C) (32-34), indicating that DNA double-strand breaks (DSBs), produced through different mechanisms by these agents, are the crucial molecular lesions for cell killing in NBS. However, the mechanism leading to NBS cell death following induction of DSBs has not been determined (e.g., no evidence for increased apoptosis has been described). Indeed, one report even showed diminished IR-induced apoptosis in leukocytes from a patient with NBS (35).

Image Theory And Applications In Bioelectromagnetics

Investigation of bioelectricity phenomena has gained recently a steadily increasing interest in medical and engineering applications. This chapter deals with the computational aspects of bioelectromagnetic interactions and their related bioelectric processes, aiming to provide a better physical understanding of the effect of functional electrical stimulation (FES) on biological tissue and to set-up models that can provide quantitative insights into this bioelectromagnetic phenomenon. These goals are achieved here by an explicit image series construction of the macroscopic electromagnetic field within the multilayer tissue. The novel image series expansion scheme, outlined here for qua-sistatic Green's function in multilayer media, utilizes a unique and explicit recursive representation for Green's function. Our recursive construction convergences under rather general constraints on the media parameters. The usefulness and effectiveness of the proposed analysis is demonstrated through...

Genetic Instability And Dna Repair

An issue that has been hotly debated in the literature is whether FA cells are sensitive toward ionizing radiation (reviewed recently in Ref. 75). Within the context of the conditioning regimen for bone marrow transplantation, there has been a longstanding clinical impression of increased radiosensitivity of patients with FA who also seem to tolerate cyclophosphamide less well than patients who do not have FA. However, in vitro studies with FA cells have yielded conflicting results. An unpublished study from our laboratory shows that FA fibroblasts of all known complementation groups respond to increasing x-ray doses in the same way as control cells (Fig. 2). Moreover, when fibroblasts from patients with ataxia-telangiectasia (which are known to be highly radiosensitive) are taken as positive controls, studies from our laboratory provide no evidence for increased radiosensitivity of FA fibroblasts under in vitro conditions. A surprising result has been obtained when primary...

Occupational exposure

The effects of low-grade protracted exposure to radiation in older age as seen in nuclear workers and individuals living in high-risk areas are at least intriguing. Several case-controlled studies reported an increased risk of MM among nuclear workers exposed to external penetrating ionizing radiation. In the international combined analyses of mortality data on 95,673 workers, more than 85.4 men, employed for at least 6 months in the nuclear industry in the United States, United Kingdom, and Canada, were monitored for external exposure to ionizing radiation. The analyses covered a total of 2,124,526 person-years at risk and 15,825 deaths, 3976 of which were due to cancer. Among the 31 specific types of cancers studied, a significant association was observed only for MM (P 0.037 44 deaths).76 In the Sellafield British nuclear plant the cancer mortality and incidence among 14,282 workers employed between 1947 and 1975 were studied up to 1988. Overall cancer mortality and incidence were...

Degradation Processes In Biodegradable Polymers

Another aspect to be considered is the fact that biomedical materials need sterilization before being implanted. Sterilization can be performed using heat, steam, gas (ethylene oxide, EtO), or ionizing radiation, mainly g or p. Each of these sterilization methods may have an effect on the material degradation, but sterilization by radiation requires high doses of high-energy radiation, resulting in some cases in polymer crosslinking and degradation. g sterilization was shown to reduce significantly the molecular weight of poly(lactide-glycolide) polymers,6 but cold-cycle EtOH sterilization did not cause any changes in the molecular weight of polylactides.8 Mechanical stress may also affect the degradation, either as a result of loading under service or due to residual stress arising during manufacturing, but this type of degradation is more significant on materials subjected to mechanical stress such as sutures, scaffolds for tissue engineering, and fixation devices.6

Summary and Future Development

In vitro studies have evaluated the additive and synergistic antitumor activity of HDACi with many agents including cytotoxics, targeted molecules, and radiation. Considerable interest has been focused on combinations with DNA methyltransferase inhibitors like 5 aza-2'deoxycytidine (decitabine) and retinoic acid receptor (RAR)-targeted drugs. Furthermore, enhancement of apoptosis has been shown with traditional cytotoxics like the topoiso-merase II agents and taxanes, TRAIL (tumor necrosis factor related apoptosis inducing ligand), CDK (cyclin dependent kinase) inhibitors, Hsp-90 antagonists like 17-AAG proteosome inhibitors and enhanced radio sensitivity to ionizing radiation 11,138 . Combination clinical studies of HDACi with retinoic acid 139 and conventional cytotoxics like carboplatin, paclitaxel, capecitabine and gemc-itabine 140-143 have already been shown to be feasible in the clinic. Although improved response rates have yet to be demonstrated, trial characteristics make it...

Scientific Foundations

Electricity and magnetism are like two different aspects of the phenomenon called electromagnetism, one of the fundamental forces of the universe. Every electrical charge causes an invisible electric field to exist around itself. An electric field pushes or pulls against other charges. Like charges repel each other opposite charges attract. Electrical charges that are moving, or electric fields that change over time, also create (induce) magnetic fields. In turn, magnetic fields that change over time make electric fields. A ray of visible light or a radio wave (both electromagnetic waves) is really a pair of ever-changing electric and magnetic fields that bring each other into being as they move together through space. This self-creation and propulsion system is why light can travel across the vacuum of space and does not need a medium like a wave in ocean water.

Antiangiogenesis agents

There is a theoretical concern when considering combining radiation with agents that inhibit angiogenesis. Because these agents may act by reducing blood vessel number and function within the tumor resulting in hypoxia, and because it is well known that the biologic effect of ionizing radiation is diminished in the presence of tissue hypoxia, it is possible that the administration of angiogenesis agents prior to or concurrently with radiotherapy may reduce the efficacy of radiation and result in inferior clinical outcome. There are a few preclinical experiments that have addressed this issue, and the results have been somewhat mixed. Teicher et al. demonstrated that the administration of antiangiogenic agents prior to chemotherapy or radiotherapy reduced the number and size of lung metastasis formed from the primary tumor in a Lewis lung carcinoma model when compared to either therapeutic modality alone (14). Lund et al. examined the effect of TNP-470, a synthetic analog of fumagillin...

Signal transduction inhibitors

The ErbB family of growth factor receptors is well characterized and has been generating increasing interest as a target for cancer therapeutics. The family, which consists of epidermal growth factor receptor (EGFR), HER-2, HER-3, and HER-4, is over-expressed in a significant proportion of human cancers (25,26). In breast cancer, for example, 30 of tumors overexpress EGFR or HER-2, and 90 express HER-3. In addition, overexpression of the ErbB receptors is correlated with poorer prognosis and decreased survival compared to patients with tumors that are ErbB receptor negative. Most importantly, specific blockade of ErbB members EGFR and HER-2 has a number of antineoplastic effects. These effects include complete growth inhibition in vitro, a progressive diminution of colony-forming ability, and sensitization to the lethal effects of ionizing radiation. Ionizing radiation activates both EGFR and downstream signaling involving the cytoprotective mitogen-activated protein kinase (MAPK)...

Cell cycle inhibitors

Eukaryotic cells respond to DNA damage by eliciting multiple synchronous signals that can trigger both repair and apoptotic processes (76). The specific intracellular pathways that trigger apoptosis and suppress DNA repair are unclear however, one critical mediator of the cellular response to DNA damage is the tumor suppressor gene product p53, which is linked to cell cycle arrest, DNA repair, and programmed cell death after DNA damage due to ionizing radiation (77-79). Among the downstream p53-regulated genes is p21WAF1, which inhibits cyclin CDK complexes causing cell cycle arrest in G1 phase (80). Because ionizing radiation leads to G1 arrest and apoptosis by a p53-dependent pathway, reintroduction of functional wild-type p53 genes into tumor cells is a potential strategy to improve radiation sensitivity. Using direct local delivery, recombinant viral vectors with wild-type p53 have been successfully reintroduced into tumor cells in preclinical studies, and this strategy is being...

Clinical trials targeting the egfr her1

Currently, large randomized trials in patients with NSCLC, prostate cancer, and bladder cancer are testing whether ZD1839 alters the response rate, time to tumor progression, and toxicity of standard chemotherapy. Preclinical laboratory data have indicated that ZD1839 is synergistic with ionizing radiation against breast cancer cell lines (44). Preliminary data suggest that ZD1839 alone is also effective against HER-2-overexpressing breast cancer cells that also express EGFR and has an additive effect against these cells when combined with trastuzumab (45). These observations imply a possible role for small molecule EGFR tyrosine kinase inhibitors in patients with breast cancer whose tumors overexpress HER-2.

DNA Damage Checkpoint Genes

DNA damage and replication checkpoint response pathways in eukaryotes. (A) Components of a checkpoint signaling pathway arising from the replication block or DNA damage (DSB SSB) are shown. Radl7-Rad9-Husl-Radl and MREll-Rad53-Nbsl-ATM complexes can act as sensors after double-strand breaks. Similarly, Radl7-Rad9-Husl-Radl and ATR-ATRIP complexes act after replication or other types of DNA damage. BRCAl claspin can act as adaptors in the DNA damage response. Chkl Chk2 act as effector kinases. (B) ATR-Chkl or ATR-Chk2 can be activated after replication stress or UV damage and cause phosphorylation of Cdc25 or p53 for checkpoint responses. However, after ionizing radiation, ATM can activate Chkl Chk2, which phosphorylate Mus8l, p53, or Brcal to perform checkpoint and repair responses. Fig. 7. DNA damage and replication checkpoint response pathways in eukaryotes. (A) Components of a checkpoint signaling pathway arising from the replication block or DNA damage (DSB SSB) are shown....

Tumors of the Meninges

Meningiomas in children are rare, constituting only 3 of pediatric brain tumors no female predominance is noted. They are more common during the second decade of life but may occur at any age, including in fetuses and infants. In a significant number of children, meningiomas are associated with neurofibromatosis type 2 (NF2), often in the absence of a family history. Ionizing radiation is a potential risk for the development of a menin-

Effect of Bcrabl on DNA Repair and Genomic Stability

In the first study investigating such a relationship, Deutsch et al. (66) looked at the effects of BCR-ABL on the catalytic subunit, DNA-PKCS, of the DNA-PK complex formed with the heterodimeric Ku protein. Repair of DSBs by the DNA-PK-dependent pathway nonhomologous end-joining (NHEJ) recombination is the preferred pathway utilized by human cells (67), and in mice, NHEJ deficiency accelerates lymphoma formation and promotes the development of soft tissue sarcomas that possess clonal amplifications, deletions, and translocations (68,69). In BCR-ABL-expressing cells (including primary CML cells), levels of DNA-PKCS were markedly downregulated (66) and were reversed by proteasome inhibitors, suggesting the activation of a BCR-ABL-dependent pathway leading to enhanced proteasome-dependent protein degradation (66). Downregulation of DNA-PKCS levels was associated with a higher frequency of chromosomal abnormalities after exposure of BCR-ABL-expressing cells to ionizing radiation (IR) and...

Bioinstrumentation Design

Measurement signals are always corrupted by noise in a biomedical instrumentation system. Interference noise occurs when unwanted signals are introduced into the system by outside sources, e.g. power lines and transmitted radio and television electromagnetic waves. This kind of noise is effectively reduced by careful attention to the circuit's wiring configuration to minimize coupling effects. Interference noise is introduced by power lines (50 or 60 Hz), fluorescent lights, AM FM radio broadcasts, computer clock oscillators, laboratory equipment, cellular phones, etc. Electromagnetic energy radiating from noise sources is injected into the amplifier circuit or into the patient by capacitive and or inductive coupling. Even the action potentials from nerve conduction in the patient generate noise at the sensor amplifier interface. Filters are used to reduce the noise and to maximize the signal-to-noise (S N) ratio at the input of the A D converter.

Maintenance Of The Germ Line

Related research indicates that ionizing radiation transiently blocks Ocell proliferation and induces programmed cell death (i.e., apoptosis) in the germ line (46). In some organisms, apoptosis serves to eliminate cells that have been extensively damaged. The genetic control of apoptosis in the somatic cells of C. elegans has been extensively studied (47,48) and is meditated by the same core apoptotic machinery (e.g., ced-9, ced-4, ced-3) as employed in the germ line. The dual responses of cell cycle arrest and apoptosis upon irradiation suggest that an active checkpoint is operative in the C. elegans germ line. Indeed, these phenotypes are reversed by mutations in three genes, mrt-2, rad-5, and him-7 that is, irradiation of these mutants does not inhibit germ line proliferation and induces apoptosis as it does in wild type. Interestingly, these mutants were isolated using three different types of mutant hunts namely, for a mortal germ line (mrt-2 42 ), for somatic cell radiation...

The Molecular Biology of Cellular Aging

An important unifying principle that may explain many of these observations is the telomere hypothesis of cell aging and immortalization.34,35 This model proposes that differentiated somatic cells such as fibroblasts lack the enzyme telomerase. As a result, each round of cell division results in a loss of DNA from the lagging strand of the 3' linear end, perhaps due to the end replication problem. This is in line with numerous reports that cultured mortal cells lose telomeric DNA at a rate of about 50-200bp per cell doubling.36 When perhaps only a single chromosome end has lost repeat sequences, the cell may detect a linear DNA end that is indistinguishable from a double strand break. As a result, the cell may exit the cell cycle in a DNA damage checkpoint arrest, similar to that seen in cells exposed to ionizing radiation.37 This arrest is dependent on p53 and is designated Mortality-1 (M1).38 Genotoxic stress induces a unique pattern of gene expression that induces intracellular...

Dna Repair And Telomeric Function

Telomerase-Deficient Mice with Short Telomeres Are Hypersensitive to Ionizing Radiation Double-strand breaks (DSBs) are generated by reactive by-products of oxygen metabolism, by exposure to ionizing radiation, and in V(D)J recombination in lymphocytes. Efficient DSB DNA repair machinery eliminates these breaks, which might otherwise cause increased death or tumorigenesis. There is increasing evidence that short telomeres result in increased organismal sensitivity to ionizing radiation. Short telomeres render yeast and Caenorhabditis elegans more radiosensitive. Based on work in yeast, it has been proposed that short telomeres may directly impair the efficiency of DSBs generated by ionizing radiation, since they may be the storage sites for DNA-repair proteins (90,91), although this has not been formally addressed to date. Terc ' mice with progressively shorter telomeres provide a unique system with which to address whether there is a causal relationship between short telomeres and...

Structural Chromosomal Aberrations

Chromosomal translocations are structural aberrations characterized by relocations of chromosomal segments within one or among different chromosomes. As chromosomal translocations are relatively stable structural changes (76-78), they would be expected to accumulate with age. Several investigators have found that the increase in translocation frequencies in a nonsmoking normal population follows a curvilinear relationship with age (79,80). Although ionizing radiation is known to induce chromosomal translocations, it cannot alone account for the strong age-related increase of chromosomal translocations (80). It has been argued that age may play a role in an individual's response to radiation exposure, as the capacity of DNA repair mechanisms may decline with age (81,82). However, it has been demonstrated that the susceptibility to translocation formation induced by acute (83) and chronic (80) ionizing radiation does not change with age. Apparently, other factors are involved in this...

Vertebral Morphometry and Fractures

Fan-array DXA spine imaging is one of the newer applications for DXA. The spine can be imaged from T4 to L5 in the lateral or PA projection. DXA spine imaging can be performed in seconds to minutes, depending on the scan mode, but always at a fraction of the radiation exposure of conventional spine radiographs.

Application Of Mri To Study Metabolic Disorders

MRI is based on the principles of nuclear magnetic resonance, a spectroscopic technique used by scientists to obtain microscopic chemical and physical information about molecules (1). MRI became widely available in the mid 1980s and has become the preferred imaging modality for clinical and research anatomical imaging (2). Unlike computed tomography (CT) scanning, MRI can be obtained in multiple planes and can produce highly resolute images. By using different pulse sequences for image acquisition, tissue contrast can be manipulated to yield images that are suited for specific purposes. The lack of ionizing radiation makes it safe for repeated scanning of an individual and particularly for the scanning of infants and young children.

Studies in MS and Other Conditions

Hyperbaric oxygen is an accepted therapy for a limited number of specific medical conditions. For example, it is an effective treatment for burns and severe infections. Other rare uses included decompression sickness (as a result of deep-sea diving), carbon monoxide poisoning, air bubbles in the blood stream caused by medical procedures, and tissue injury caused by radiation exposure.

Crosssectional Studies Of Quantitative Mr Techniques In People With The Clinical Diagnosis Of Ad

Cerebral blood volume MR measurements using contrast agents indicate a reduction in temporoparietal blood volume in patients with AD (38-40). Another technique sensitive to cerebral blood flow but does not require injection of contrast agents is arterial spin labeling (ASL). Significant blood flow reductions were identified in the temporal, parietal, frontal, and posterior cingulate cortices of patients with AD relative to controls (41). ASL is an appealing technique for blood flow measurements because it does not require contrast injection or ionizing radiation. Studies comparing the accuracy of ASL to nuclear medicine imaging modalities as surrogate markers for blood flow changes in AD are needed.

Tamoxifen and Breast Cancer Prevention

Thirty years ago, tamoxifen was shown to prevent the induction and promotion of carcinogen-induced mammary cancer in rats.92,200 Similarly, tamoxifen was also shown to prevent the development of mammary cancer induced by ionizing radiation in rats. These laboratory observations, coupled with the emerging preliminary clinical observation that

Artery Calcifications

Cardiac CT is extremely sensitive in the detection and quite accurate in the quantification of coronary artery calcifications 9 . In addition, cardiac CT is a noninvasive and quick method that is easy to perform. Thus, cardiac CT is currently regarded as the standard-of-care for the detection and quantification of coronary artery calcifications although the radiation exposure of this technique must be taken into account. However, there was recently a controversial debate about the most suitable cardiac CT imaging technique for coronary artery calcium scoring. The arguments advanced in discussing the pros and cons of the potential techniques pertain to temporal resolution, spatial resolution, image noise, radiation exposure, availability and reference values (see below) 10 .

Ataxiatelangiectasia

The first clue that defects in the ATM gene disrupt normal cellular responses to DNA damage were provided by case reports of AT patients who died from severe reactions to radiation therapy directed at their lymphoid tumors (33-37). Although not unusually susceptible to the induction of DNA breaks by ionizing radiation (38,39), cultured cells from AT patients are typically three to five times more sensitive than control cells to the cytotoxic effects of ionizing radiation as well as other agents that induce DSBs (40-44). AT radiosensitivity is also manifest by an increase in number of chromosomal aberrations induced by ionizing radiation or radiomimetic agents (reviewed in Ref. 23). Cells from AT homozygotes can be exquisitely sensitive to the cytotoxic effects of ionizing radiation, but they differ from most other radiosensitive mammalian cells in that their ability to repair DNA damage appears to be largely intact. Base excision repair is apparently normal (45), and multiple...

Rsk Reduction in Women with Inherited Predisposition to Breast cancer

The actuarial cumulative probability of breast cancer was 35 at age 40 years. The increased risk of breast cancer is evident at 10 years following treatment, with further cases seen 15 years or more into follow-up. The long-term risk of developing breast cancer falls with increasing age at radiation exposure, demonstrating the predisposition to the development of breast cancer to be due to the exposure of mammary tissue to radiation during the pubertal growth phase. A reasonable recommendation for these patients is biannual mammographic screening beginning 8 years post-radiation until age 30 years and annually thereafter 109 .

Ku At The Mammalian Telomere

In contrast to the action of yeast Ku in response to DNA-damaging agents (73), human Ku does not dissociate from the telomere upon exposure to ionizing radiation and the radiomimetic drug phleomycin (60). Since Ku is distributed throughout the mammalian nucleus, apparently its recruitment from the telomere to sites of DNA repair is not necessary (73).

The Measurement of Light or Radiant Energy

Technically light and radiant energy are not the same. Radiant energy is considered to be all electromagnetic energy, whereas historically, light refers to the part of the electromagnetic spectrum that is visible to the human eye (between the wavelengths of 380 and 750 nm). Thus, the strict definition of light is based on human sensitivity to radiant energy. However, the term light is generally used to define radiant energy detected by physiological systems in humans and nonhumans, and the term light will be used interchangeably with the term radiant energy in this chapter. An understanding of light (or radiant energy) as a stimulus is essential if biological responses to light are to be understood.

Tumor vascular window model

The tumor vascular window model allows for measurement of tumor vascularity by use of fluorescent and light microscopy. A window is placed over the dorsal skin fold of a mouse and tumors are implanted within the window to allow microscopic visualization of tumor blood vessels (Fig. 3). The vascular window model facilitates direct measurement of the vascular response to ionizing radiation in several tumor models. Radiation induces dose- and time-dependent injury to tumor blood vessels within the window. Figure 3 shows blood vessels within GL261 (A and B) and B16F0 (C and D) implanted into the dorsal skin fold window model. Blood vessels developed over 1 wk, at which time they were treated with ionizing radiation. Figure 3E shows that the radioresistant GL261 tumor vessels had a minimal response to 6 Gy, whereas the radiosensitive B16F0 tumors showed elimination of microvasculature in response to 3 Gy.

Preclinical data of gemcitabine as a radiosensitizer

Although the exact mechanism by which gemcitabine serves to sensitize cells to damage from ionizing radiation is not well defined, there is burgeoning literature on the subject. Nucleoside analogs including fludarabine, cladrabine, and gemcitabine are felt to be attractive agents to combine with radiation for multiple reasons. First of all, these agents are S phase specific (16) and as such should be selectively toxic to proliferating cells. This may serve to decrease the cell proliferation that can occur during fractionated radiotherapy. Second, cell cycle redistribution induced by these agents can serve to improve cell kill by allowing more cells to be treated in the more sensitive parts of the cell cycle (17). As DNA synthesis inhibitors these drugs may act to inhibit the repair of radiation-induced DNA damage (18). Finally, as this class of drugs acts as DNA chain terminators, if incorporated into areas where DNA repair has occurred after radiation, they may cause the triggering...

Epidemiology Etiology and Biology

However, some studies suggest a multitude of possible inciting factors that may predispose a patient to develop osteosarcoma. Ionizing radiation, which is used to treat cancer, has been linked in a dose-dependent manner to secondary osteosarcoma 5 . Treatment of radiation-induced osteosarcoma may be difficult however, outcome for these patients can be similar to that of de novo osteosarcoma if surgical resection of the primary is possible 6 . Chemical agents, such as methylcholan-threne, beryllium oxide, and zinc beryllium oxide have been implicated in the pathogenesis of osteosarcoma 7, 8 . Viral infection has also been identified as a cause of osteosarcoma in animal models 9, 10 . In addition, while patients and families often remember trauma to the site of disease, there is no evidence that injury to bone is a predisposing factor. In adults, but not children, cases of osteosarcoma have been reported occurring in the area of bone infarcts 11, 12 .

Risk Factors and Cancer

Ionizing radiation is a universal but weak carcinogen.1,39 However, cumulative exposures from medical diagnostic and treatment procedures, commercial, occupational sources, or waste increase the risk of cancer. Leukemias and cancers of the breast, lung, and thyroid are typical but cancers of the stomach, colon, and bladder, and potentially any human tumor may be seen. Radiation can cause most types of cancer, especially myelogenous leukemia and cancers of the breast, thyroid, and lung. Some cancers that have not been linked to radiation include chronic lymphocytic leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, and cancers of the cervix, testis, prostate, and pancreas. Despite the massive radiation contamination resulting from the nuclear reactor accidents at Chernobyl and Chelyabinsk thus far the only well-documented increase in cancer is childhood thyroid cancer.40 Finally, genetic predisposition can increase the risk of developing cancer by exposure to radiation, as in the...

Adenoviral p53 Gene Transfer with Radiation Therapy in NSCLC

At the present time, delivery of Ad-p53 requires direct injection into the tumor with guidance by bronchoscopy or CT scan. This delivery system allows high concentrations of vector to be administered in and around the injected tumor but it is not able to target micrometastatic disease. Another strategy therefore would be to combine Ad-p53 with radiation therapy to try to enhance locoregional control without increasing toxicity. Currently, despite improvements in radiation and chemoradiation, the locoregional control of locally advanced NSCLC remains poor. One- and 2-yr pathologic control rates following radiation or chemoradiation are estimated to be less than 20 (25). Preclinical studies with Ad-p53 indicate that delivery of wild-type p53 to p53-deficient cells, in both in vitro and in vivo models, increases tumor sensitivity to ionizing radiation (26-29). Because of these preclinical results, we evaluated the potential impact of Ad-p53 (INGN 201) in combination with radiation in a...

Classification Of Aa Based On Etiology And Pathophysiologic Mechanisms

Bone marrow aplasia is a well-known toxicity of ionizing radiation. Myeloablation using 7-radiation is used therapeutically as a conditioning regimen for stem cell transplantation. The bone marrow is affected directly by 7-rays, and secondarily by a- and p-particles. Certain cell types, such as lymphocytes, are very sensitive and are killed directly, while hematopoietic progenitors require cell division for severe damage thus, mitotically active cells are most sensitive. The onset and severity of pancytopenia is dose dependent. However, the regeneration capacity of the irradiated marrow is remarkable, likely due to the presence of quiescent, more resistant stem cells. While the exact LD50 dose is not precisely known in humans, 1.5-2 Gy of whole body radiation can induce marrow aplasia. The dose of 4.5 Gy (Shields-Warren number) has been estimated to constitute the LD50.1147 The estimation of marrow toxicity is hampered by the toxicity to other organ systems that may limit survival. At...

Dna Damage And Repair

The sources of DNA damage are protean. Environmental agents may act as mutagens, thus increasing the likelihood of the occurrence of mutations. Known agents in this category include ultraviolet (UV) light (the major source being exposure to sunlight), ionizing radiation, cigarette smoke, and various carcinogens such as asbestos and possible dietary factors. Whereas exposure to environmental factors frequently can be reduced or minimized by behavioral modification, other sources of DNA alteration are unavoidable errors during DNA replication (which occur with each cell division), damage from by-products of normal cellular metabolism (including reactive oxygen species superoxide anions, hydroxyol radicals, and hydrogen peroxide derived from oxidative respiration), and products of lipid peroxidation. Other weak mutagens, such as thermally promoted hydrolysis of nucleotide residues by water, may occur under physiological conditions. Deamination results in base substitutions, such as the...

Other Imaging Modalities

To better understand IVUS, it is important to compare it to other cardiovascular imaging. X-ray angiography remains the gold standard for coronary arteries. Its main advantages are high spatial resolution (0.15 mm) and relatively low cost compared to other modalities (23). The main drawbacks are the radiation exposure for the patient during an intervention as multiple injections of radioactive contrast agent are delivered. Also, angiography is a minimally invasive procedure using a catheter to deliver the radioactive contrast agent. Furthermore, planar X-ray imaging captures a projection of the vasculature and can often misdiagnose asymmetric lesions (23).

Ras farnesylation inhibitors

Despite the uncertainties as to the mechanism of FTI inhibition of proliferation, FTIs radiosensitize tumor cells. This effect appears to be specific to Ras transformation (69). Experimental evidence suggests that cells transformed with the activated Ras oncogene are often more resistant to cell killing by ionizing radiation (70,71). Inhibition of farnesyltransferase with FTI-277 radiosensitizes human tumor cells with H-Ras mutations, and the combination of a geranylgeranyltransferase (GGTase) with an FTI radiosensitizes human tumor cells with K-Ras mutations but not tumor cells with wildtype Ras (69,72). Thus Ras induced radioresistance can be reversed with FTIs (73). As radiosensitization is not seen in cells with wild-type Ras , the combination of FTI and fractionated radiotherapy may result in improved therapeutic index through sparing of normal tissue relative to tumor tissue.

Radiolabeled Monoclonal Antibodies

Lym-1 has been conjugated to 131I in order to effect targeted delivery of this radioactive isotope to tumor cells of B-cell origin. Although 131I-Lym-1 has been tested primarily in patients with advanced NHL, the antibody has been given to several patients with B-CLL. Twenty-five patients with previously treated, advanced B-NHL and five patients with relapsed B-CLL were treated with fractionated, low-dose 131I-Lym-1, with a goal of 300 mCi per patient (122). Thirty percent of patients developed HAMAs, but only three patients had therapy interrupted as a result. Four of the five CLL patients responded (80 ). The same group also reported that patients who responded to 131I-Lym-1 therapy enjoyed improved survival (84 vs 22 wk) (123). Radiation dosimetry studies revealed a lower tumor radiation dose and a higher liver radiation exposure in CLL patients, compared with NHL patients, resulting in a lower therapeutic index for patients with CLL (124). Toxicity was acceptable, and the...

Chemoradiation

The medical uses of ionizing radiation have expanded dramatically since Wilhelm Roentgen first discovered it at the end of the last century. In particular, it has proven to be an effective agent in the ongoing battle against cancer. It is presumed that the essential target for radiation is cellular DNA where it acts through the formation of free radicals to directly or indirectly cause double-stranded breaks. It is these double-stranded breaks in the DNA that are felt to be the lethal lesion that malignant cells sustain from therapeutic radiation. Enhancement of tumor response is of course the main topic of this chapter and this book. Enhancement is often used as a term to imply an increase in response and in the general sense is defined by a situation in which the administration of one agent increases the effectiveness of another or when the effect of the combination is greater than expected (27). Interaction of different agents makes it difficult to characterize the exact nature of...

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