Inhibition of DNA synthesis, independent of DNA adduct formation, by benzo[a]pyrene diol epoxide in mammalian cells

Treatment of SV40-infected CV-1 cells with the ultimate carcinogen anti-benzo[a]pyrene diol epoxide (BPDE) at 1 × 10 −4 mg/ml or higher reduced the rate of viral DNA synthesis to an extent dependent on the BPDE concentration; similar reductions in cellular DNA synthesis were produced in infected and uninfected cells. Treatment of cells with BPDE, followed by removal of BPDE, at various times before infection with SV40 gave the same results. Recovery or partial recovery of DNA synthesis occurred when the BPDE concentration was below 6 × 10 −4 mg/ml; at higher concentrations the cells were killed. Simultaneously replicating viral DNA's from viruses infecting the same cells before and after BPDE treatment of the cells exhibited the same reduced rate of synthesis. The evidence indicates that covalent adducts in viral DNA are not responsible for its reduced replication rate; moreover, it is probable that an insignificant number of adducts is produced in intracellular viral DNA at BPDE concentrations that do not kill CV-1 cells. Rather, it appears likely that BPDE inhibits viral DNA synthesis by attacking cellular DNA or non-DNA targets. Caution is therefore required in relating the effects of BPDE and other carcinogens to DNA adduct formation.