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| TITLE: | Cellular Effects of Low Frequency Electromagnetic Fields | ||
| Principal Investigator |
Jerry R. Williams | Johns Hopkins University | |
| Health Relevance |
Cancer | ||
| Research Categories |
Cellular Function | Gene Expression | Cell Proliferation |
| FY95 Funds | R01ES07076 $ 299,158 | Start Date 09/28/94 | End Date 08/31/98 |
| Rationale and Summary |
There have been several claims made in the biomedical literature that exposure to low frequency
electromagnetic fields (EMF) leads to an increase in cancer risk. The epidemiological data on this
point is contradictory, and part of the skepticism which surrounds the issue derives from the absence
of any well-established mechanism by which EMF could induce oncogenic changes. Evidence
suggests that EMF fields do not lead to DNA damage or mutation. However, there are a number of
studies which show that EMF lead to increased levels of a number of mRNAs, including c-myc, c-
fos, c-jun and protein kinase C (PKC). All these genes are known to be implicated in malignant
transformation. These findings need to be reproduced. Moreover a pathway has to be established
showing the chain of events which lead from EMF exposure to gene expression.
We wish to examine the effect of EMF exposure on tumor cells with defined genetic abnormalities. We are particularly interested in small cell lung cancer lines, which have been extensively studied in this laboratory. These cells can spontaneously advance to a non-small cell phenotype. Transfection studies indicate that c-myc expression is a necessary component of this transition. In this system, EMF induction of c-myc may represent a mechanism of malignant progression. We also wish to test the hypothesis that EMF may interact with environmental mutagens. We will address this question using cells deficient in mismatch repair, testing their response to ionizing radiation and alkylating agents in the presence or absence of EMF. These cells represent a hypermutation phenotype that is relevant to multistage carcinogenesis. |
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| Experimental Design and Exposure Conditions |
The EMF exposure apparatus consists of two coil assemblies, arranged so that either can be
activated. The experimenter does not know which cells have been exposed and which have been
subjected to sham treatment.
The cell lines to be used are the human leukemic line HL60 and the human small cell lung cancer lines NCI H82, NCI H209 and NCI H249. EMF effects on c-myc expression have been noted in HL 60 cells. The lung cancer lines have been extensively studied in this laboratory with regard to c-myc regulation. Six human colon cancer lines will also be studied. Three of these are deficient in the mismatch repair pathway. EMF effects have been noted in HL 60 cells at 5µT, 60 Hz after 20 minutes. These exposure conditions will be used first, though we plan to study the effect of field strength and frequency over the ranges 0.5 - 500 µT and 15 - 120 Hz respectively. The exposure system can be ramped to eliminate transients; a comparison between cells exposed to ramped and unramped fields will be made. Animal studies will be considered if the in vitro results warrant. The animal model has yet to be selected. |
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| Quality Assurance Measures |
Background fields in the exposure room have been monitored and found to be negligible in the area where the coils are situated. Stray fields were monitored by the installing engineer. The two exposure units do not interfere with each other. The experiments will be conducted double blind, in that the experimenter will not know which cells have been exposed to an EMF field and which are the sham-treated controls - nor will the individual who scores for biological response know treatment received by each group. Ionizing radiation will be used as a positive control for mutagenesis and cell cycle delay studies. Chemical treatments such as TPA and retinoic acid which are known to induce or repress the genes of interest will also be used as controls. | ||
| Results and Discussion |
Studies have been completed comparing the mutability of cells with and without mismatch repair
capacity. The repair deficient cells have a much higher spontaneous rate of mutation at the hprt
locus. They are also more prone to radiation-induced mutation.
Similarly the small cell lung cancer (SCLC) cells have been investigated for spontaneous and radiation-induced transition to a non small cell (NSCLC) phenotype. Low doses (up to 3 Gy) of ionizing radiation enhance the fraction of NSCLC recovered. However these NSCLC may be more radioresistant, raising the possibility that ionizing radiation is acting as a selective agent. The relative contributions of radiation induced mutations and selection in this system has yet to be determined. |
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| Recent Publications |
None. | ||