Temporary cell cycle arrest in neural and extraneural developing rat tissues after exposure to methyl--and ethylnitrosourea.
8 days old rats were exposed to 20 or 100 mg/kg b.w. of either Methylnitrosourea (MNU) or Ethylnitrosourea (ENU), followed by injection of 10 muCi/g b.w. of (3H-methyl)-Thymidine. After a 100 mg dose of MNU or ENU in both neural and extraneural tissues a total inhibition of S-phase radioactivity is observed that lasts longer for MNU than for ENU. Moreover reappearance of S-phase cells in the neural tissues is later (36-48 h) than in the extraneural tissues (24-36 h) for both drugs. In both neural and extraneural tissues reappearance of S-phase cells is consistently found to occur about 12 h earlier than recurrence of M-phase cells. After a 20 mg dose of MNU or ENU in both neural and extraneural tissues a clear decrease in S-phase radioactivity is found after a 6 h' interval only. There are only slight differences between the various tissues and drugs. In developing rat tissues there is obviously a trend for both mitotic activity and S-phase radioactivity to decrease with increasing single doses of MNU or ENU. Our results point to an arrest in or before entering the S-phase of the cells involved. The more pronounced cytotoxic activity of MNU as compared to ENU is discussed. Recurrence of DNA synthesis and re-entrance of damaged cells into their cycle prior to the elimination of altered bases from DNA might be of importance for the problem of oncogenesis.
D000818:Animals; D000831:Animals, Newborn; D005038:Ethylnitrosourea / Q000494:pharmacology; D008770:Methylnitrosourea / Q000494:pharmacology; D008938:Mitosis / Q000187:drug effects*; D009417:Nerve Tissue / Q000187:drug effects*; D009607:Nitrosourea Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D009607:Nitrosourea Compounds; D008770:Methylnitrosourea; D005038:Ethylnitrosourea