Temporary cell cycle arrest in neural and extraneural developing rat tissues after exposure to methyl--and ethylnitrosourea

• Published in: Zeitschrift f r Krebsforschung und Klinische Onkologie 1976-05, Vol.86 (1), p.23-31
• Main Authors: Bosch, D A, Ebels, E J
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Ethylnitrosourea - pharmacology; Methylnitrosourea - pharmacology; Mitosis - drug effects; Nerve Tissue - drug effects; Nitrosourea Compounds - pharmacology; Rats; Rats, Inbred Strains
• ISSN: 0084-5353; 1432-1335
• DOI: 10.1007/BF00304931

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.