[ EMF-Link Home
| Online Store
| Comments
| Up One Level ]
| TITLE: | Magnetic Fields Effects on the Promotion of Cancer | ||
| Principal Investigator |
Craig V. Byus, Ph.D. | University of California, Riverside | |
| Health Relevance |
Cancer | ||
| Research Categories |
Toxicology in Whole Animals | Tumor Initiation/Promotion | Dermal-mice |
| FY95 Funds | R01ES06128 $151,975 | Start Date 09/30/92 | End Date 09/29/96 |
| Rationale and Summary |
The overall goal of this grant is to determine whether exposure to 60 Hz low-energy electromagnetic fields alters the incidence of cancer in a well-defined animal model. For these studies, the highly-defined two-stage model of initiation/promotion of skin carcinogenesis in the mouse is used. A low dose of a well-studied chemical carcinogen (dimethylbenzanthracine) is applied to the skin on the back of a mouse. This exposure alone will not cause any statistically significant increase in the number of skin tumors (papillomas) over the lifetime of the animal. A number of environmental chemicals have been determined to be "promoters" of tumor formation in this and other models. Thus, a promoting agent is capable of increasing markedly the incidence of papillomas following a single administration of initiating agent where application of the promoting agent itself causes no increase in cancer. Our hypothesis is that low-energy electromagnetic fields do not serve as initiating or DNA damaging agents, however, they could serve as promoting or copromoting agents in the normal etiology of human cancer. We are administering a low dose of a chemical tumor promoting agent and assessing the ability of the electromagnetic field administration to cause the appearance of tumors in these animals. This is a very well-controlled, highly-defined study both in the quantitation of the tumors which occur as well as in the exposure of the animals to electromagnetic fields. The extremely low background incidence of tumors in this model, coupled with the easily observed tumors which appear on the back of the mice, make this model quantitative in that tumor numbers and incidence can be accurately determined over the 35 week duration of the experiment. We are also testing a series of biochemical correlates to determine the ability of the cell to respond to low-energy electromagnetic fields. The enzyme ornithine decarboxylase, appears to increase reproducibly in response to exposure to magnetic fields of low intensity. Thus, we are studying the regulation of this enzyme and the mechanism by which the fields may interact or control this enzyme activity through the altered export of the polyamine putrescine from the cell. It is hoped that the understanding of the biochemical molecular marker of field and tissue/cell interaction may ultimately lead to a better understanding of the mechanism(s) of this process. | ||
| Experimental Design and Exposure Conditions |
We are in the unique situation of having as a co-investigator, Dr. Maria M. Stuchly, Professor of
Electrical and Computer Engineering at the University of Victoria, in addition to close collaboration
with the technical expertise of W. Ross Adey, at VA Loma Linda.
For the animal exposure system, we use an apparatus designed with multiple coils arranged to produce a uniform magnetic field within a large volume, while minimizing stray fields outside the coils. The coils are bifilarly wound with a twisted-pair wire, so that any apparatus can be allocated to the active field exposure or sham exposure condition in a blind matter. The minimal heating of the air due to the coils and vibrations hence were identical for all apparatus.. The maximum flux densities in the cages in the initial experiments were 2 mT ± 10% with most of the volume within 3% of the nominal flux value. The magnetic field density in the sham exposure cages was below 0.1 µT and there was no electrical field produced by the coils. Dr. Stuchly has designed and we have recently built an in vitro exposure apparatus to study the regulation of polyamine metabolism in various cell culture cells. This is also a twisted wire system which allows us to have 4 exposure apparatus in a single incubator with a 4-log difference in dose and magnetic field between systems. This system also was designed by Dr. Stuchly and manufactured by Bob Jones in Dr. Adey’s group at VA Loma Linda. |
||
| Quality Assurance Measures |
Our in vivo exposure system was inspected by W/L Associates, Ltd., including Fred Dietrich as the engineer, contractors to the Department of Energy. In addition we have put extreme effort, as a result of the efforts of Dr. Stuchly and her engineering staff, into the design, building, and quality control of both the in vivo and in vitro exposure systems. All apparatus work in a double blind manner and are continuously monitored for temperature and field intensities during all experiments by computer controlled systems. True sham-controls are included for all field experiments in which animals and cells are placed in exposure systems which are, in fact, "energized" in an identical manner as the field itself in that a bucking current is provided in the opposite polarity to assure that exposure was a true sham. | ||
| Results and Discussion |
Our findings to date indicate that exposure to a 2 mT field for 5 hours was sufficient to cause an increase in tumor incidence when applied along with an extremely low dose of a well-defined chemical tumor promoter in the mouse two-stage model initiation-promotion. This increase in tumor incidence was highly statistically significant yet occurred only at the lowest of two doses of the chemical promoting agents employed in these experiments, At the higher, although still submaximal concentration of chemical promoting agent, there was no effect of electromagnetic field exposure upon tumorigenicity. We are currently performing an additional large animal tumor experiment designed to replicate and extend these interesting findings. We are most interested in determining the dose-response effect which may exist between field intensity and increase in tumor incidence seen when the field is supplied as a co-promoting agent. The significance of these findings, if replicated, could be important in understanding the potential health effect/risk of low- energy magnetic fields in the environment. Our investigations on the potential involvement of electromagnetic field interactions with polyamine metabolism, and in particular, putrescine or polyamine export, are also significant associations which we have made during the previous four years. It is hoped that we will be able to derive a logical, testable hypothesis involving polyamine metabolism in which the fields cause the increase in carcinogenicity seen in the animal models. | ||
| Recent Publications |
Hawel, L. III, Tjandrawinata, R.R., Fukumoto, G.H. and Byus, C.V. Biosynthesis and selective
export of 1,5-diaminopentane (cadaverine) in mycoplasma-free cultured mammalian cells. J. Biol
Chem. 269: 7412-7418 (1994).
Tjandrawinata, R.R., Hawel, L., III and Byus, C.V. Regulation of putrescine export in lipopolysaccharide IFN- -activated murine monocytic-leukemia RAW264 cells. J. Immunol. 153: 3039-3052 (1994). Hawel, L. III, Tjandrawinata, R.R. and Byus, C.V. Selective putrescine export is regulated by insulin and ornithine in Reuber H35 hepatoma cells. Biochemica Biophysica Acta 1222: 15-26. (1994). Tjandrawinata, R.R. and Byus, C.V. Regulation of the efflux of putrescine and cadaverine from rapidly growing cultured RAW 264 cells by extracellular putrescine. Biochem. J. 305: 291-299 (1995). Tjandrawinata, R.R., Hawel, L. III and Byus, C.V. Verapamil and guanine inhibit the export of putrescine in a calcium-independent manner. Biochem. Pharm. 48: 2237-2249 (1995). Byus, C.V. Alterations in ornithine decarboxylase activity: A cellular response to low-energy electromagnetic field exposure. In: Summary and Results of Radiofrequency Radiation Conference, published by U.S. Environmental Protection Agency (1995), 402-R-95-011. Byus, C.V. and Hawel, L. Review of Biological Experiments currently performed in the USA, Part I. In : Progress in Safety and Assessment of Mobile Communications. N. Kuster, editor, Chapman and Hall, Inc. (To be published, 1996). Byus, C.V. and Ma, Y. Effect of 60 Hz magnetic fields as copromoting agents in mouse two-stage model of initiation and promotion. Cancer Research (submitted). Xi, W., Stuchly, M.A., and Gandhi, O.P. Induced electric currents in models of man and rodents from 60 Mz magnetic fields. IEEE TRans. Biomed. Eng. 41: 1018-1023 (1994). Caputa, K. and Stuchly, M.A. Computer controlled system for producing uniform magnetic fields and its application in biomedical engineering. IEEE Trans. Instrum. Meas. (Accepted, 1995). |
||