Effects of the carcinogen urethane on nuclear RNA polymerase activities

Abstract

Intraperitoneal injection of male rats with a single dose of the carcinogen urethane inhibited the Mg 2+ -dependent RNA polymerase activity of isolated lung nuclei by about 50%. The inhibition was maximal 1 hr after the injection. Twenty hours after administration, the Mg 2+ -stimulated activity was again normal. The non-carcinogenic derivatives methylcarbamate and butylcarbamate had no effect on RNA polymerase activities of isolated lung nuclei. The inhibition of nuclear RNA synthesis by urethane was not due to increased hydrolysis of newly synthesized RNA, and the template activity of lung chromatin was not affected by the carcinogen. The activity of Mn 2+ + (NH 4 )SO 4 -dependent RNA polymerase activity of isolated lung nuclei was not affected by urethane injection. The two RNA polymerase activities of liver nuclei were not inhibited by the carcinogen. Mg 2+ -stimulated nuclear RNA synthesis in vitro was inhibited markedly by urethane at concentrations above 50 mM, whereas the Mg 2+ + (NH 4 ) 2 SO 4 -dependent activity was only slightly affected. In vitro RNA synthesis catalyzed by E. coli RNA polymerase was inhibited also by high concentrations of the carcinogen.