Carcinogen-mediated induction of SV40 DNA synthesis in SV40 transformed Chinese hamster embryo cells.
Exposure of SV40-transformed Chinese hamster embryo cells (line CO50) to a series of physical and chemical carcinogens (including activation-dependent and activation-independent varieties) resulted in the induction of viral DNA synthesis. The carcinogen mediated amplification of SV40 DNA was demonstrated by a highly sensitive in situ hybridization procedure for the detection of cells synthesizing SV40 DNA. Treatment of CO50 cells with an inhibitor of polycyclic hydrocarbon metabolism (7,8-benzoflavone) prior to the application of benzo[a]pyrene or 7,12-dimethylbenz[a]anthracene prevented the induction of SV40 DNA synthesis, indicating that the induction depends upon the metabolic activation of these compounds. Non-carcinogenic hydrocarbons were inactive under this assay. Two different protocols for determining the inducing potential of a compound are presented. The properties of this test and its possible use as a short-term assay for potential carcinogens is discussed. The possibility that the induction of SV40 DNA synthesis is a reflection of a general gene amplification phenomenon mediated by carcinogens is discussed.
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D000818:Animals; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology*; D002472:Cell Transformation, Viral / Q000187:drug effects*; D002999:Clone Cells; D006224:Cricetinae; D003412:Cricetulus; D004279:DNA, Viral / Q000096:biosynthesis*; D004622:Embryo, Mammalian; D005260:Female; D011247:Pregnancy; D013539:Simian virus 40 / Q000378:metabolism*
D001580:Benzopyrenes; D002273:Carcinogens; D004279:DNA, Viral; D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide