Carcinogen-mediated induction of SV40 DNA synthesis in SV40 transformed Chinese hamster embryo cells

Exposure of SV40-transformed Chinese hamster embryo cells (lineCO50) to a series of physical and chemical carcinogens (includingactivation-dependent and activation-independent varieties) resultedin the induction of viral DNA synthesis. The carcinogen mediatedamplification of SV40 DNA was demonstrated by a highly sensitivein situ hybridization procedure for the detection of cells synthesizingSV40 DNA. Treatment of CO50 cells with an inhibitor of polycyclichydrocarbon metabolism (7,8-benzoflavone) prior to the applicationof benzo[a]pyrene or 7,12-dimethyl-benz[a]anthracene preventedthe induction of SV40 DNA synthesis, indicating that the inductiondepends upon the metabolic activation of these compounds. Non-carcinogenichydrocarbons were inactive under this assay. Two different protocolsfor determining the inducing potential of a compound are presented.The properties of this test and its possible use as a short-termassay for potential carcinogens is discussed. The possibilitythat the induction of SV40 DNA synthesis is a reflection ofa general gene amplification phenomenon mediated by carcinogensis discussed.