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暴露于甲基和乙基亚硝基脲后,发育中的大鼠神经和非神经组织出现暂时的细胞周期停滞。

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

作者信息

Bosch D A, Ebels E J

出版信息

Z Krebsforsch Klin Onkol Cancer Res Clin Oncol. 1976 May 3;86(1):23-31. doi: 10.1007/BF00304931.

Abstract

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.

摘要

将8日龄大鼠暴露于20或100毫克/千克体重的甲基亚硝基脲(MNU)或乙基亚硝基脲(ENU)中,随后注射10微居里/克体重的(3H-甲基)-胸腺嘧啶核苷。在给予100毫克剂量的MNU或ENU后,在神经组织和神经外组织中均观察到S期放射性完全抑制,MNU的这种抑制持续时间比ENU更长。此外,两种药物处理后,神经组织中S期细胞的重新出现时间(36 - 48小时)比神经外组织(24 - 36小时)更晚。在神经组织和神经外组织中,均发现S期细胞的重新出现比M期细胞的再次出现早约12小时。在给予20毫克剂量的MNU或ENU后,仅在6小时的间隔后,神经组织和神经外组织中的S期放射性就出现明显下降。不同组织和药物之间只有细微差异。在发育中的大鼠组织中,随着MNU或ENU单次剂量的增加,有丝分裂活性和S期放射性明显呈下降趋势。我们的结果表明,所涉及的细胞在进入S期时或之前就被阻滞。讨论了MNU与ENU相比更明显的细胞毒性活性。在从DNA中消除改变的碱基之前,DNA合成的重新出现以及受损细胞重新进入其细胞周期可能对肿瘤发生问题具有重要意义。

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