Biomedical subjects

R Kavet

Publications and source records attributed to R Kavet.

At least 37 records · Page 2Linked to original sources

PubMed1999

Predicting cancer rates in astronauts from animal carcinogenesis studies and cellular markers.

The radiation space environment includes particles such as protons and multiple species of heavy ions, with much of the exposure to these radiations occurring at extremely low average dose-rates. Limitations in databases needed to predict cancer hazards in human beings from such radiations are significant and currently do not provide confidence that such predictions are acceptably precise or accurate. In this article, we outline the need for animal carcinogenesis data based on a more sophisticated understanding of the dose-response relationship for induction of cancer and correlative cellular endpoints by representative space radiations. We stress the need for a model that can interrelate human and animal carcinogenesis data with cellular mechanisms. Using a broad model for dose-response patterns which we term the "subalpha-alpha-omega (SAO) model", we explore examples in the literature for radiation-induced cancer and for radiation-induced cellular events to illustrate the need for data that define the dose-response patterns more precisely over specific dose ranges, with special attention to low dose, low dose-rate exposure. We present data for multiple endpoints in cells, which vary in their radiosensitivity, that also support the proposed model. We have measured induction of complex chromosome aberrations in multiple cell types by two space radiations, Fe-ions and protons, and compared these to photons delivered at high dose-rate or low dose-rate. Our data demonstrate that at least three factors modulate the relative efficacy of Fe-ions compared to photons: (i) intrinsic radiosensitivity of irradiated cells; (ii) dose-rate; and (iii) another unspecified effect perhaps related to reparability of DNA lesions. These factors can produce respectively up to at least 7-, 6- and 3-fold variability. These data demonstrate the need to understand better the role of intrinsic radiosensitivity and dose-rate effects in mammalian cell response to ionizing radiation. Such understanding is critical in extrapolating databases between cellular response, animal carcinogenesis and human carcinogenesis, and we suggest that the SAO model is a useful tool for such extrapolation.

Animals↗

PubMed1999

Magnetic field exposure and cardiovascular disease mortality among electric utility workers.

Laboratory studies suggest that electric and magnetic field exposure may affect heart rate and heart rate variability. Epidemiologic evidence indicates that depressed heart rate variability is associated with reduced survival from coronary heart disease as well as increased risk of developing coronary heart disease. The authors examined mortality from cardiovascular disease in relation to occupational magnetic field exposure among a cohort of 138,903 male electric utility workers from five US companies over the period 1950-1988. Cardiovascular disease deaths were categorized as arrhythmia related (n = 212), acute myocardial infarction (n = 4,238), atherosclerosis (n = 142), or chronic coronary heart disease (n = 2,210). Exposure was classified by duration of work in jobs with elevated magnetic field exposure and indices of cumulative magnetic field exposure. Adjusting for age, year, race, social class, and active work status, longer duration in jobs with elevated magnetic field exposure was associated with increased risk of death from arrhythmia-related conditions and acute myocardial infarction. Indices of magnetic field exposure were consistently related to mortality from arrhythmia and acute myocardial infarction, with mortality rate ratios of 1.5-3.3 in the uppermost categories. No gradients in risk were found for atherosclerosis or for chronic coronary heart disease. These data suggest a possible association between occupational magnetic fields and arrhythmia-related heart disease.

Cardiovascular Diseases↗

PubMed1999

Determinants of power-frequency magnetic fields in residences located away from overhead power lines.

The Wertheimer-Leeper wire code, originally developed as a surrogate for magnetic-field exposure, has been associated with childhood leukemia in several epidemiologic investigations. However, these and other studies indicate that most between-residence variability in measured magnetic fields remains unexplained by wire codes. To better understand this remaining variability, engineering and demographic data were examined for 333 underground (UG) and very-low current configuration (VLCC) single-family or duplex residences, selected from a database of nearly 1000 residences specifically because their magnetic fields are most likely affected negligibly by overhead power lines. Using linear regression techniques, four factors predictive of the log-transformed residential field were identified: the square-root of the 24-h average net service drop current (this current is equivalent to the current in the grounding system), the log of the number of service drops on the same secondary serving the residence, residence age (four categories), and area type (rural, suburban, or urban). Complete data on ground current and service drops, the two factors with the strongest individual relationships to measured fields, were available for only half of the residences in the sample. However, these data were determined to be "missing at random" according to established statistical criteria. The full-sample or "composite" models thus relied on a method similar to regression imputation, accounting for missing data with binary dummy variables. When applied to the samples from which they were derived, these models accounted for 25% of the variance of the log-spot-measured magnetic field values in the full sample, while models that considered only those residences with complete data (n = 167) explained about 35%. The model validated well against a sample of 201 ordinary low current configuration (OLCC) homes selected from the same database.

Child↗

PubMed1999

Lack of effect of a 60 Hz magnetic field on biomarkers of tumor promotion in the skin of SENCAR mice.

It has been proposed that extremely low frequency magnetic fields may enhance tumorigenesis through a co-promotional mechanism. This hypothesis has been further tested using the two-stage model of mouse skin carcinogenesis, i.e. 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced promotion of skin carcinogenesis in mice initiated by a single subcarcinogenic dose of 7,12-dimethylbenz[a]anthracene. Experimentation utilized three different doses of TPA within its dose-response range (0.85, 1.70 or 3.40 nmol) and examined the following early biomarkers of tumor promotion after 1, 2 and 5 weeks of promotion: increases in epidermal thickness and the labeling index of epidermal cells, induction of epidermal ornithine decarboxylase activity and down-regulation of epidermal protein kinase C activity. Mice exposed to a 60 Hz magnetic field having a flux density of 2 mT for 6 h/day for 5 days/week were compared with mice exposed to an ambient magnetic field. Within the sensitivity limits of the biomarker methodology and the exposure parameters employed, no consistent, statistically significant effects indicative of promotion or co-promotion by the magnetic field were demonstrated.

Animals↗

PubMed1999

The relationship between electromagnetic field and light exposures to melatonin and breast cancer risk: a review of the relevant literature.

Worldwide, breast cancer is the most common malignancy accounting for 20-32% of all female cancers. This review summarizes the peer-reviewed, published data pertinent to the hypothesis that increased breast cancer in industrialized countries is related to the increased use of electricity [Stevens, R.G., S. Davis 1996]. That hypothesis specifically proposes that increased exposure to light at night and electromagnetic fields (EMF) reduce melatonin production. Because some studies have shown that melatonin suppresses mammary tumorigenesis in rats and blocks estrogen-induced proliferation of human breast cancer cells in vitro, it is reasoned that decreased melatonin production leads to increased risk of breast cancer. To evaluate this hypothesis, the paper reviews epidemiological data on associations between electricity and breast cancer, and assesses the data on the effects of EMF exposure on melatonin physiology in both laboratory animals and humans. In addition, the results on the effects of melatonin on in vivo carcinogenesis in animals are detailed along with the controlled in vitro studies on melatonin's effects on human breast cancer cell lines. The literature is evaluated for strength of evidence, inter-relationships between various lines of evidence, and gaps in our knowledge. Based on the published data, it is currently unclear if EMF and electric light exposure are significant risk factors for breast cancer, but further study appears warranted. Given the ubiquitous nature of EMF and artificial light exposure along with the high incidence of breast cancer, even a small risk would have a substantial public health impact.

Animals↗

PubMed1998

Inconsistent suppression of nocturnal pineal melatonin synthesis and serum melatonin levels in rats exposed to pulsed DC magnetic fields.

The purpose of these experiments was to determine whether the exposure of rats at night to pulsed DC magnetic fields (MF) would influence the nocturnal production and secretion of melatonin, as indicated by pineal N-acetyltransferase (NAT) activity (the rate limiting enzyme in melatonin production) and pineal and serum melatonin levels. By using a computer-driven exposure system, 15 experiments were conducted. MF exposure onset was always during the night, with the duration of exposure varying from 15 to 120 min. A variety of field strengths, ranging from 50 to 500 microT (0.5 to 5.0 G) were used with the bulk of the studies being conducted using a 100 microT (1.0 G) field. During the interval of DC MF exposure, the field was turned on and off at 1-s intervals with a rise/fall time constant of 5 ms. Because the studies were performed during the night, all procedures were carried out under weak red light (intensity of <5 microW/cm2). At the conclusion of each study, a blood sample and the pineal gland were collected for analysis of serum melatonin titers and pineal NAT and melatonin levels. The outcome of individual studies varied. Of the 23 cases in which pineal NAT activity, pineal melatonin, and serum melatonin levels were measured, the following results were obtained; in 5 cases (21.7%) pineal NAT activity was depressed, in 2 cases (8.7%) studies pineal melatonin levels were lowered, and in 10 cases (43.5%) serum melatonin concentrations were reduced. Never was there a measured rise in any of the end points that were considered in this study. The magnitudes of the reductions were not correlated with field strength (i.e., no dose-response relationships were apparent), and likewise the reductions could not be correlated with the season of the year (experiments conducted at 12-month intervals under identical exposure conditions yielded different results). Duration of exposure also seemed not to be a factor in the degree of melatonin suppression. The inconsistency of the results does not permit the conclusion that pineal melatonin production or release are routinely influenced by pulsed DC MF exposure. In the current series of studies, a suppression of serum melatonin sometimes occurred in the absence of any apparent change in the synthesis of this indoleamine within the pineal gland (no alteration in either pineal NAT activity or pineal melatonin levels). Because melatonin is a direct free radical scavenger, the drop in serum melatonin could theoretically be explained by an increased uptake of melatonin by tissues that were experiencing augmented levels of free radicals as a consequence of MF exposure. This hypothetical possibly requires additional experimental documentation.

Animals↗

PubMed1998

Lack of a co-promoting effect of a 60 Hz magnetic field on skin tumorigenesis in SENCAR mice.

It has been proposed that extremely low frequency (ELF) magnetic fields may enhance tumorigenesis through a co-promotional mechanism. This hypothesis has been further tested using the two-stage model of mouse skin carcinogenesis, i.e. 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced promotion of skin tumors in mice initiated by a single subcarcinogenic dose of 7,12-dimethylbenz[a]anthracene. Experimentation described herein utilized the SENCAR mouse and examined the effect of a magnetic field on skin tumor promotion induced by three different doses of TPA within its dose-response range, i.e. 0.85, 1.70 or 3.40 nmol, administered twice per week. SENCAR mice (56/treatment group) were exposed to a 60 Hz magnetic field having a flux density of 2 mT for 6 h/day for 5 days/week and compared with mice exposed to the ambient magnetic field. Tumor incidence and multiplicity were monitored weekly for 23 weeks of TPA promotion. Statistical evaluation of the effects of the magnetic field on tumor incidence and multiplicity did not reveal any statistically significant effects; thus, within the sensitivity limits imposed by the animal model and the exposure parameters employed, no promotional or co-promotional effect of a 2 mT magnetic field on skin tumor development in SENCAR mice could be demonstrated.

Animals↗

PubMed1998

Prediction of nocturnal plasma melatonin from morning urinary measures.

A growing literature indicates that blood levels of the hormone melatonin may have important implications for human health and well-being. Melatonin is synthesized and released into the general circulation at night, however, and it is seldom feasible to draw blood samples at night in epidemiological studies. There is some evidence that levels of urinary melatonin and of 6-sulfatoxymelatonin (aMT6s), the major metabolite of melatonin, accurately reflect nocturnal plasma melatonin. If this is the case, urinary assays could be powerful tools for epidemiological studies. A laboratory-based study was performed to examine the relationships between nocturnal plasma melatonin, morning urinary melatonin, and morning urinary aMT6s levels in 78 men. The relationship between total nocturnal plasma melatonin and both urinary aMT6s corrected for creatinine and urinary melatonin is significant. Combining the two urinary measures accounts for 72% of the variance in total plasma melatonin. Peak nocturnal plasma melatonin also was significantly related to urinary melatonin and to aMT6s. The urinary measures show good sensitivity and specificity in identifying individual differences in nocturnal plasma melatonin levels. These results support the inclusion of morning urine samples to assess the contribution of the hormone melatonin in occupational or residential studies involving healthy, young men.

Adolescent↗

PubMed1997

Wire codes, magnetic fields, and childhood cancer.

Childhood cancer has been modestly associated with wire codes, an exposure surrogate for power frequency magnetic fields, but less consistently with measured fields. We analyzed data on the population distribution of wire codes and their relationship with several measured magnetic field metrics. In a given geographic area, there is a marked trend for decreased prevalence from low to high wire code categories, but there are differences between areas. For average measured fields, there is a positive relationship between the mean of the distributions and wire codes but a large overlap among the categories. Better discrimination is obtained for the extremes of the measurement values when comparing the highest and the lowest wire code categories. Instability of measurements, intermittent fields, or other exposure conditions do not appear to provide a viable explanation for the difference between wire codes and magnetic with respect to the strength and consistency of their respective association with childhood cancer.

Brain Neoplasms↗

PubMed1997

Summary and evaluation of guidelines for occupational exposure to power frequency electric and magnetic fields.

Major U.S. and international guidelines for limiting occupational exposures to EMF are evaluated. These safety guidelines are designed to prevent short-term adverse effects by maintaining bulk-tissue current densities below 10 mA m(-2) (rms). Above this level, effects of induced currents and electric fields can include stimulation of neural and cardiac tissues. The models and input data used by guideline-setting organizations to relate 50/60-Hz magnetic-field exposures to induced current densities differ significantly. In order to develop a better understanding of such differences, the current densities derived from exposure guideline models are compared to minimum thresholds for cardiac stimulation and fibrillation. The nominal minimum thresholds for cardiac stimulation and ventricular fibrillation are 100 times and 200 times greater, respectively, than the current density of 10 mA m(-2) used as a dosimetric limit. However, the assumed relationship between the 10 mA m(-2) dose limit and magnetic field exposure limits introduces additional uncertainty. The ratios between the threshold for cardiac stimulation and the calculated induced current density at the exposure limit vary between a low of 50 and a high of 526, depending upon the guideline. These ratios, as indicators of implicit safety factors, are larger than those recommended to protect against adverse effects of induced current density, including cardiac stimulation, in magnetic resonance imaging or against adverse effects of toxic chemical exposures. This review and assessment of EMF occupational exposure guidelines suggests that several scientific and compliance issues remain ambiguous or unresolved. Recommendations are made for guideline organizations to strengthen and clarify the scientific basis for the guideline process. These recommendations include the documentation of supporting data, development of operational definitions for guidelines, examination of dosimetric models, clarification of safety factors, and identification of high priority topics for future research.

Biophysics↗

PubMed1997

Testing electromagnetic fields for potential carcinogenic activity: a critical review of animal models.

In order to assess the potential of electromagnetic fields (EMF) to influence the process of carcinogenesis, it will be necessary to supplement epidemiological studies with controlled laboratory studies in animals. There are now a number of suitable assays available that focus on different histopathological forms of cancer and on different stages of carcinogenesis--induction, promotion, progression. In this review we discuss eight major systems in the context of this generalized carcinogenesis paradigm. Our aim is to bring together what is currently known about the biology of carcinogenesis in these systems in order to provide a context for evaluating EMF results as they become available. We also critically discuss EMF test results that have so far been obtained in the animal models reviewed. Most of the 19 completed studies identified were negative. However, suggestive positive results were reported in three promotion assays (in rat mammary gland, in rat liver, and in mouse skin), and in one multigeneration study in mice. Results in the rat liver assay and in the multigeneration study have only been reported in abstract form and cannot be adequately evaluated. Positive results reported in both the rat mammary gland and the mouse skin systems are of weak statistical significance and have not been independently replicated. However, it may be of interest that effects in both systems appear primarily to involve the progression stage of carcinogenesis. We suggest that more definitive conclusions as to the carcinogenic potential of EMF may require expanded test protocols that reinforce traditional carcinogenesis end points with biochemical or other parameters reflective of biological processes known to be associated with carcinogenesis in the different systems.

Animals↗

PubMed1997

Comparison of coupling of humans to electric and magnetic fields with frequencies between 100 Hz and 100 kHz.

Recent laboratory and epidemiological results have stimulated interest in the hypothesis that human beings may exhibit biological responses to magnetic and/or electric field transients with frequencies in the range between 100 Hz and 100 kHz. Much can be learned about the response of a system to a transient stimulation by understanding its response to sinusoidal disturbances over the entire frequency range of interest. Thus, the main effort of this paper was to compare the strengths of the electric fields induced in homogeneous ellipsoidal models by uniform 100 Hz through 100 kHz electric and magnetic fields. Over this frequency range, external electric fields of about 25-2000 V/m (depending primarily on the orientation of the body relative to the field) are required to induce electric fields inside models of adults and children that are similar in strength to those induced by an external 1 microT magnetic field. Additional analysis indicates that electric fields induced by uniform external electric and magnetic fields and by the nonuniform electric and magnetic fields produced by idealized point sources will not differ by more than a factor of two until the sources are brought close to the body. Published data on electric and magnetic field transients in residential environments indicate that, for most field orientations, the magnetic component will induce stronger electric fields inside adults and children than the electric component. This conclusion is also true for the currents induced in humans by typical levels of 60 Hz electric and magnetic fields in U.S. residences.

Adult↗

PubMed1997

Can low-level 50/60 Hz electric and magnetic fields cause biological effects?

Some epidemiological studies have suggested that exposure to ambient, low-level 50/60 Hz electric and magnetic fields (EMFs) increases risk of disease. Whether this association has a causal basis depends in part on whether the electrical, chemical and mechanical "signals" induced within living cells by ambient EMFs are detectable in the complex milieu of voltages, currents and forces present within the living organism. Magnetic responsiveness has been found in some animals and bacteria; aquatic animals (e.g. sharks and rays) can sense weak electric fields. We outline the physics of several mechanisms by which EMFs may interact: (1) Energy transfer by acceleration of ions and charged proteins modifies cell membranes and receptor proteins; however, EMF energies are far below those typical of biomolecules in the cell. (2) Electric fields induced inside the body exert force on electric charges and electric moments; however, these forces are considerably smaller than typical biological forces. (3) The magnetic moments of ferromagnetic particles and free radical molecules interact with magnetic fields, but magnetic-moment sensory cells have not been found in humans, and modification of radical recombination rates by EMFs in a biological system is highly problematic. (4) Resonant interactions involve EMFs driving vibrational or orbital transitions in ion-biomolecule complexes; these mechanisms conflict with accepted physics, and many experimental tests have not found the predicted effects. (5) Temporal averaging or spatial summation can improve the ratio of "signal" to "noise" in any system, but this "mechanism" requires biological structures and neural processes having the necessary capabilities of EMF detection and temporal averaging that have not been found in humans. In summary, biological effects in humans due to extremely low-frequency EMFs of the order of those found in residential environments [< or = 2 microT (< or = 20 mG)] are implausible based on current understanding of physics and biology. Biological effects in humans at higher fields [> 10 microT (> 100 mG)] might reach plausibility as a result of time-averaging in combination with a magnetic-moment transduction mechanism; but even here, neither specialized EMF transduction structures nor appropriate averaging networks have been demonstrated. The bypothesis that the epidemiological associations observed between 50/60 Hz EMFs and disease reflect a causal relationship is not supported by what is known about mechanisms.

Animals↗

PubMed1996

EMF and current cancer concepts.

Exposure to power frequency electric and magnetic fields (EMF) is ubiquitous, and a body of epidemiologic studies has produced evidence suggestive of a possible link between EMF exposure and cancer of several types. This paper provides a perspective that holds key findings in the EMF literature against the background of important models and established principles in cancer biology. It is intended primarily for scientists whose expertise lies outside of cancer biology and animal bioassays. Current thinking holds that carcinogenesis is a multistep process that requires at least two genotoxic events in its critical path but that is facilitated by nongenotoxic proliferative effects on target cells. EMF, which itself is not believed to be genotoxic, could influence carcinogenesis if it exerted either direct or indirect effects on target cell turnover. Such effects could operate through receptor-mediated or nonreceptor-mediated pathways. However, effects relevant to carcinogenesis have not been confirmed, and a mode of action for EMF has not been determined. Chronic bioassays in rodents are in progress to examine the potential carcinogenicity of EMFs. EMF research has the opportunity to capitalize on the recent major advances in our understanding of carcinogenic processes.

Animals↗

PubMed1993

Depressive symptoms and headaches in relation to proximity of residence to an alternating-current transmission line right-of-way.

Electric power transmission lines have become objects of public controversy. Hypotheses have linked neurobehavioral effects to the electric and magnetic fields that these lines produce. The authors conducted a telephone interview survey in November 1987 to assess the prevalence of depressive symptoms and headache in relation to proximity of residence to an alternating-current transmission line in the United States. Proximity to the line, defined as residing on a property abutting the right-of-way or being able to see the towers from one's house or yard, was positively associated with a measure of depressive symptoms. The association was not explained by demographic variables associated with depression or by attitudes about power lines or other environmental issues. The estimated prevalence odds ratio was 2.8 (95% confidence interval (CI) 1.6-5.1). The estimate did not change appreciably when the definitions of depressive symptoms or of proximity to the line were altered. Nonmigraine headaches had a weaker association with proximity to the line (odds ratio = 1.5, 95% CI 0.76-2.8), and self-reported migraine headaches exhibited no association (odds ratio = 0.99, 95% CI 0.29-3.4). Additional studies of psychological and behavioral measures should be conducted in relation to electric and magnetic fields, with a strong emphasis on improved exposure assessment.

Adult↗

PubMed1992

Magnetic field exposure assessment for adult residents of Maine who live near and far away from overhead transmission lines.

Sixty-Hz magnetic field exposures were measured for 45 adult residents of Maine. Thirty of the subjects resided near rights-of-way (ROWs) with either 345- and 115-kV transmission lines, or ROWs with only 115-kV transmission lines; fifteen resided far from any transmission lines. Personal exposure data for a single 24-hour period was acquired with the EMDEX. The EMDEX's event-marker button was used to partition exposures into Home and Away components. Also, three area measurements were taken for each subject during the personal exposure measurement period: 1) 24-hr fixed-site bedroom measurement with a second EMDEX; 2) Spot measurements in at least three rooms of every residence; and 3) Spot measurements outside each residence. Residence near transmission lines highly loaded during the measurement period was associated with increased Home and Total exposure relative to a far-away population. Average exposure level while away from home was uniform (at about 2 mG) throughout the study population. On a quantitative level, Home exposure was correlated equivalently with Spot-In (r = .70) and the 24-hr fixed site measurement (r = .68). Correlations of area measurements with Total exposure were weaker because of the dilution effect of Away exposure (r = .64 for Spot-In; r = .61 for 24-h Bedroom). Away and Home exposures were not correlated (r = .14), which reinforced our confidence that the participants used the EMDEX correctly. The data suggest the need for caution before inferences are drawn about total personal exposure from area measurements. The study demonstrates the feasibility of obtaining valid measures of magnetic-field exposure with the personal exposure monitors that have been developed.

Adult↗

PubMed1992

The effects of continuous exposure to 20-kHz sawtooth magnetic fields on the litters of CD-1 mice.

Mated CD-1 mice were exposed to 20-kHz sawtooth magnetic fields similar to those associated with video display terminals (VDT). Four groups of animals were continuously exposed from day 1 to day 18 of pregnancy to field strengths of 0, 3.6, 17, or 200 microT. There were no less than 185 mated dams in each exposure group. On day 18, the dams were sacrificed and assessed for weight gain and pregnancy. The litters were evaluated for numbers of implantations, fetal deaths and resorptions, gross external, visceral and skeletal malformations, and fetal weights. There were no less than 140 pregnant females in each group, and there were no significant differences between any of the exposure groups and the sham group (0 microT) for any of the end points. The results of this study do not support the hypothesis that the 20-kHz VLF magnetic fields associated with video display terminals are teratogenic in mammals.

Abnormalities, Radiation-Induced↗

PubMed1992

A review of the literature on potential reproductive and developmental toxicity of electric and magnetic fields.

The potential of electric and magnetic fields to adversely affect the health of the human population is an issue which continues to receive a great deal of attention in both public and scientific forums. One of the critical issues is the possibility that such fields may adversely affect the reproductive process. Numerous studies investigating the potential of electric and/or magnetic fields to alter reproduction in vertebrates have been conducted. These studies have, in many instances, yielded seemingly contradictory results. A number of epidemiological studies have been conducted as well. This review of the literature examines relevant studies and attempts to draw biologically rational conclusions from them. The studies are ordered in broad categories based upon both classification of the species studied (i.e. submammalian, mammalian exclusive of man and human) and the agent used (i.e. extremely low frequency electric, very low frequency electric, and magnetic fields). From our review we conclude that laboratory experimental and epidemiological results to date have not yielded conclusive data to support the contention that such fields induce adverse reproductive effects under the test or environmental conditions studied. Additional studies may, however, be warranted to clarify some of the experimental results obtained.

Animals↗