Abstract |
During the last several years, the authors have been studying the effects of chemicals on the inhibition and enhancement of oncogenic cell transformation in C3H10T1/2Cl8 mouse embryo fibroblasts (C3H10T1/2 cells). The findings, summarized in Table 1, indicate that many diverse chemicals can affect oncogenic cell transformation. In general, their mechanisms of action seem to be at the level of the enzymes which are involved in the metabolic activation of the carcinogens used to transform the cells. Specifically, 7,8-benzoflavone, 1,2-naphthoquinone, and phenanthrene-9,10- quinone inhibit cell transformation by inhibiting cytochrome P-450 mediated oxidation (11, 13). Benz(a)anthracene, 5,6-benzoflavone, phenobarbital, and pregnenolone-16-alpha-carbonitrile enhance cell transformation by inducing the complex of cytochrome P-450 mixed-function oxidases and increase the ability C3H10T1/2 cells to metabolize carcinogens (14). Cyclohexane, cyclohexane oxide, 1,2-dihydronaphthalene, stryene oxide and 1,2,3,4-tetrahydronaphthalene-1,2-oxide enhance cell transformation by inhibiting epoxide hydratase and thus allow increased levels of active arene oxides to accumulate in the cells (13). |