Early effects of dimethylnitrosamine on protein chain initiation and postmicrosomal polyadenylic acid-containing RNA content in mouse liver.
A mouse liver S-30 system was used to study the early effects of dimethylnitrosamine (DMNA) on polypeptide chain initiation and messenger RNA content. The inhibition of protein synthesis after DMNA administration was associated with a reduced capacity of the S-30 system to form 80S ribosomal initiation complexes. The binding of formylatable methionyl transfer RNA to polysomes was also depressed. The initiation defect was detectable in the assay system slightly later than the decrease in protein synthesis. Addition of mRNA stimulated both translation and 80S initiation complex formation but could not fully restore the activity of the S-30 system from DMNA-treated mice. A loss of poly(A)+ RNA from the postmicrosomal subfraction of the S-30 fraction was observed as early as 15 min after DMNA administration. Later, polyriboadenylic acid also decreased in the microsomal fraction. Monosomes accumulating in response to DMNA treatment were deficient in mRNA as measured by polyriboadenylic acid analysis. Conversely, the proportion of polyriboadenylic acid in the remaining polysomes increased, indicating that the mRNA had become less densely occupied with ribosomes.
D000818:Animals; D004128:Dimethylnitrosamine / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010442:Peptide Chain Initiation, Translational / Q000187:drug effects*; D011061:Poly A / Q000378:metabolism; D012313:RNA / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D012333:RNA, Messenger; D011061:Poly A; D012313:RNA; D004128:Dimethylnitrosamine