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| TITLE: | Effects of EMF on Proto-oncogene DNA Binding Activity During Brain Development | ||
| Principal Investigator |
Keith Pennypacker, Ph.D. | Laboratory of Environmental Neurosciences, NIEHS | |
| Health Relevance |
Neuro-behavioral Dysfunction/ brain development | ||
| Research Categories |
Toxicology studies using whole animals | Neuro-behavioral | Gene Expression |
| FY95 Funds | DIR-9 $ 30,000 | Start Date 10/93 | End Date 9/95 |
| Rationale and Summary |
There have been reports that exposure to magnetic fields might affect the nervous system causing neurobehavioral dysfunction. Previous studies from our laboratory showed that during early postnatal development, the brain contains high levels of AP-1 transcription factor DNA binding activity and c-Jun transcription factor. The elevated content of these factors which regulate gene transcription appears to be correlated with cellular proliferation/differentiation in the brain. Thus, AP-1 DNA binding activity can serve as a sensitive index for early brain development. The purpose of this project is to examine the effects of EMF on the developing brain. Pregnant rats were exposed to different levels of EMF (0, 20mG, 2G and 10G) during the gestation period. Pups from different EMF exposed mothers were sacrificed at postnatal day 3 and the brain levels of AP-1 DNA binding activity and c-Jun immunoreactivity were determined. No change in c-Jun binding activity was detected in the brains from rats exposed to EMF. The AP-1 binding activities were lower in EMF-exposed groups than the control group, although there was no clear dose- response relationship. This finding suggests that EMF affects the expression of certain genes during brain development by modulating the expression of AP-1 transcription factors. | ||
| Experimental Design and Exposure Conditions |
The Sprague-Dawley rats that were utilized in the study "Evaluate the toxic
and carcinogenic potential of 60Hz magnetic fields in laboratory animals for
the National Toxicology Program" were studied in this proposal. In these
experiments conducted in IIT Research Institute in Chicago, several pups were
not used and were designated to be sacrificed. This study utilized these
additional rats. The pregnant rats were exposed to continuous (18.5
hours/day) or intermittent (one hour on/one hour off during the 18.5 hour
exposure period) fields of EMF during the entire pregnancy and during the
postnatal period. Ten rat pups at postnatal day 3 were sacrificed from groups
of rats exposed of EMF. Five groups of rat pups were studied:
A): Control B): 20 mGauss continuous exposure C): 2 Gauss continuous exposure D): 10 Gauss intermittent exposure E): 10 Gauss continuous exposure Brains were frozen in dry ice and brought back to NIEHS. Western blot analysis was used to determine levels of c-Jun. Gel-shift mobility assay was used to determine the AP-1 DNA binding activity. |
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| Quality Assurance Measures |
The exposure fields were independently verified by the National Institute for Standards and Technology (NIST). All culture work was done on coded samples and the codes were broken only after all work had been completed. | ||
| Results and Discussion |
Pregnant rats were exposed to different levels of EMF during the gestation
period. Pups from different EMF exposed mothers were sacrificed at postnatal
day 3 and the brain levels of AP-1 DNA binding activity and c-Jun
immunoreactivity were determined. No changes were revealed for c-Jun
immunoreactivity among the various groups. However, AP-1 DNA binding
activity was affected in the brains from rats exposed to EMF. Except for the
intermittently-exposed group (D), the AP-1 DNA binding activities of the
other three treated groups were lower (15-25%) than that of the control group
(A). Although the 2G-exposed group exhibited the least amount of AP-1
activity, there is no clear dose-response relationship among the different
exposed groups. Earlier studies from our laboratory showed that AP-1 DNA
binding activity is elevated and may be important in brain development.
Therefore, the decrease in the AP-1 binding activity obtained from this study
suggest that EMF affects neuronal development during the gestational period by
influencing the expression of certain genes which are regulated by these
transcriptional factors.
This avenue of research will not be continued. |
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| Recent Publications |
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