Time course of the effects of AAF on mouse liver nucleic acid synthesis and its modification by inhibitors

Abstract

A single dose of 2-acetamidofluorene (AAF) was found to produce a rapid inhibition of DNA and RNA synthesis in male mouse liver. RNA synthesis recovered by 7 h and DNA synthesis at about 36 h. There were peaks of RNA synthesis at 20, 24 and 54 h and there was a peak of DNA synthesis at 55 h. Measurements of RNA synthesis in isolated liver nuclei indicated that changes in the synthesis of the nucleic acid were not due to pool size changes but either to changes in template or RNA polymerase activity. Sucrose gradient analysis of RNA demonstrated that ribosomal and transfer RNA synthesis in the liver were affected equally by AAF. Hydroxyurea given within 3 h of AAF was found to delay the recovery of RNA synthesis and actinomycin D at or before 30 h inhibited the AAF-induced stimulation of DNA synthesis.