EFFECT OF CAFFEINE ON CYTOTOXICITY, MUTAGENESIS, AND SISTER-CHROMATID EXCHANGES IN CHINESE-HAMSTER CELLS TREATED WITH DIHYDRODIOL EPOXIDE DERIVATIVES OF BENZO[A]PYRENE

The effect of caffeine on Chinese hamster V79 cells after treatment with the highly mutagenic (±)-7β,8α-dihydroxy-9α,10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, and the weaker mutagen (±)-7β,8α-dihydroxy-9β,10β-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene, B[a]P-diol-epoxide II, was studied at both the biological and molecular levels. Caffeine, at nontoxic dose levels, caused a synergistic reduction in cell survival induced by both isomers and also inhibited DNA elongation as measured by alkaline sucrose-gradient analysis of nascent DNA. However, caffeine did not affect the induction of either ouabain-resistant mutants or sister-chromatid exchanges by either isomer. These results suggest that enhanced cell killing by caffeine in benzo[a]pyrene-diol-epoxide treated V79 cells may be related to caffeine's inhibitory effect on DNA elongation. However, inhibition of DNA elongation by caffeine did not influence the resulting induced levels of mutagenesis or sister-chromatid exchanges. © 1979.