Influence of 3-methylcholanthrene on liver nucleolar and nucleoplasmic activities of protein kinases and RNA polymerases.

The experiments were designed to investigate some details of the action of 3-methylcholanthrene (3-MC) on the regulation of transcription. After a single intraperitoneal dose of 3-MC a significant increase in the activities of both nucleolar and nucleoplasmic protein kinases in hepatic cells of young rats was found. The maximal stimulation took place 24 hr after the administration of 3-MC and the extent of activation was much greater in the nucleolar fraction. There is a significant elevation of the activities of both functional forms, free and template-engaged, of RNA polymerase A 24 hr after a single injection of 3-MC. Free and engaged forms of extranucleolar RNA polymerase B show a different behaviour: after 24 hr of 3-MC administration the engaged form is markedly enhanced while the activity of the free enzyme shows a significant decrease. The more moderate increase in total RNA polymerase B activity is obviously preceded by a transfer of the enzyme from 'free' to 'engaged' form. Since the enhancement of protein kinase activities was accompanied by the stimulation of nuclear RNA polymerases we suggest that both kinds of enzymes are involved in an epigenetic mechanism of the inducing action of 3-MC on cytochrome P1-450.