The effect of EMF on the regulation of thec-fos gene.
Item
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Title
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The effect of EMF on the regulation of thec-fos gene.
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Identifier
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AAI9720132
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identifier
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9720132
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Creator
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Rao, Sharmila.
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Contributor
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Adviser: Ann S. Henderson
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Date
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1997
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Molecular | Biology, Cell | Chemistry, Biochemistry
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Abstract
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The present research was designed to test a proposed role for signal transduction in the response of cells to environmentally relevant electromagnetic fields (EMFs). Two approaches were taken. The first determined if defined upstream regulatory regions of the c-fos gene were critical; the second compared the effects of EMF exposure and the tumor promoting phorbal ester, TPA, on the regulation of c-fos. HeLa cells were transiently transfected with plasmids containing various portions of the c-fos promoter complex coupled with the prokaryotic reporter gene chloramphenicol acetyl transferase (CAT). Levels of CAT activity were used as an indirect marker relative to the response of the promoter to the fields. CAT expression, driven by the construct containing +42 to {dollar}-{dollar}700 base pairs, was above background levels following 5 minutes of EMF exposure, reached a maximum activity ({dollar}\sim{dollar}25%) by 20 minutes and returned to basal levels after 40 minutes of exposure. Deletion analysis of the upstream DNA showed that a 138 bp region from -363 to -225 (containing the SRE/AP1site) is important in the response of cells to EMFs. This region is sensitive to several mitogenic factors, including TPA. Studies that compared the activities of TPA with EMF showed that they initiated similar pathways. This was supported by evidence that EMF affects on cells, like TPA, required both protein kinase C (PKC) and protein kinase A (PKA). Further, EMF exposure resulted in an increase in the uptake of {dollar}\sp{lcub}32{rcub}{dollar}P by Fos protein by 50%. This research demonstrates that EMF affects the regulation of the c-fos gene and uses signaling pathways similar to that of TPA.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
