Modulation of transcription in rat liver nuclei in vitro by a diol epoxide of benzo[a]pyrene.

Treatment of isolated rat liver nuclei with 7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene, the ultimate carcinogenic metabolite of benzo[a]pyrene, resulted in inhibition of transcription as measured by radioactive precursor incorporation into RNA. The mechanism of inhibition as analyzed by use of different types of inhibitors suggested that the carcinogen acted on both the major components of transcription machinery, that is, the template chromatin and the enzyme RNA polymerases. This action correlates well with the observations made after administration of benzo[a]pyrene to rats.