Differential Effects of Urethan on the Transcriptional Activity of Chromatin from Regenerating Liver¹ Free

The effects of urethan, administered to male rats at various times after partial hepatectomy, on the capacity of soluble chromatin to serve as a template in vitro for Escherichia coli RNA polymerase were measured. The ability of a single i.p. dose of 1 mg of urethan per g to alter the in vitro transcriptional activity of chromatin isolated from regenerating liver was dependent upon the time after the removal of 70% of the liver at which urethan was administered. The carcinogen had no detectable effect on the ability of chromatin to serve as a template for RNA synthesis, as measured by the incorporation of both adenosine triphosphate-¹⁴C and guanosine triphosphate-³H into RNA, when the tissue was exposed to urethan during the prereplicative phase of liver regeneration. However, when urethan was injected 18 hr postsurgery and the chromatin was isolated 27 to 28 hr later, the template activity of these preparations measured by maximum reaction velocities was depressed 35% as evaluated by the quantity of adenosine monophosphate incorporated and 60% as determined by the amount of guanosine monophosphate utilized. The results indicate that the genome is preferentially susceptible to the action of urethan during the period of DNA replication and that the product of RNA polymerase transcribed from urethan-altered chromatin is rich in adenosine monophosphate relative to guanosine monophosphate.