title: The effect of modifiers of microsomal enzymes on chemical oncogenesis in cultures of C3H mouse cell lines.
abstract: Two cell lines, both derived from the C3H mouse and each having different responses (oncogenic and cytotoxic) to polycyclic aromatic hydrocarbon oncogens, were studied with respect to their drug-metabolizing enzymes. The 10T1/2CL8 cells (a C3H mouse embryo fibroblastic cell line) were much more effective in converting 3-methylcholanthrene (3-MC) to 3-MC water-soluble metabolites, 3-MC phenols, and 3-MC-bound cellular macromolecules than were CVP3SC6 cells (a new line of C3H mouse adult ventral prostate fibroblasts). Basal aryl hydrocarbon hydroxylase activity was higher in 10T1/2CL8 cells than in CVP3SC6 cells, while the reverse was found for epoxide hydrase activity (using 3-methylcholanthrene-11, 12-oxide as substrate. 3-MC or benz(a)anthracene induced epoxide hydrase activity in both cell lines to about the same extent. 3-MC did not induce aryl hydrocarbon hydroxylase activity in CVP3SC6 cells. Aryl hydrocarbon hydroxylase activity was markedly induced in both cell lines by benz(a)anthracene and was slightly induced in 10T1/2CL8 cells by 3-MC. In a chemical oncogenesis cell culture system, transformation of 10T1/2CL8 cells mediated by 3-MC could be increased two- to threefold by treating the cell cultures with: either benz(a)anthracene, styrene oxide, cyclohexene oxide, or 1,2,3,4-tetrahydrona=phthalene-1,2-oxide; or with cyclohexene or 1,2-dihydrona-phthalene, alkene precursors of cyclohexene oxide and 1,2,3,4-tetrahydronaphthalene-1,2-oxide, respectively. When 10T1/2CL8 cells were treated with a combination of  benz(a)anthracene and cyclohexene, 3-MC-mediated transformation was increased 7.8-fold. CVP3SC6 cells that were not transformed by 3-MC or other hydrocarbon oncogens were transformed by a combined treatment with benz(a)anthracene, 1,2-dihydronaphthalene, and 3-MC.
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D001551:Benz(a)Anthracenes / Q000378:metabolism / Q000494:pharmacology; D002273:Carcinogens / Q000378:metabolism*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D003510:Cyclohexanes / Q000494:pharmacology; D004357:Drug Synergism; D004790:Enzyme Induction; D004851:Epoxide Hydrolases / Q000378:metabolism; D004988:Ethers, Cyclic / Q000494:pharmacology; D008748:Methylcholanthrene / Q000378:metabolism; D008861:Microsomes / Q000201:enzymology*; D009281:Naphthalenes / Q000494:pharmacology; D013343:Styrenes / Q000494:pharmacology
chemical_list: D001551:Benz(a)Anthracenes; D002273:Carcinogens; D003510:Cyclohexanes; D004988:Ethers, Cyclic; D009281:Naphthalenes; D013343:Styrenes; D008748:Methylcholanthrene; D001189:Aryl Hydrocarbon Hydroxylases; D004851:Epoxide Hydrolases