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器官特异性遗传毒性和致癌性。

Organ specific genotoxicity and carcinogenicity.

作者信息

Pool B L, Schmezer P, Tompa A, Brendler S Y

机构信息

Institute for Toxicology and Chemotherapy, German Cancer Research Center, Heidelberg.

出版信息

Prog Clin Biol Res. 1990;340D:33-41.

PMID:2371304
Abstract
  1. The in vitro studies showed that organ specific metabolic activation does not appear to play a predominant role for the in vivo activities of the studied nitrosamines 2. The in vivo studies following 1 h exposure of rats with the nitrosamines can differentiate between organs susceptible for genotoxicity and and those which are not. Nontarget organs in carcinogenicity can not be identified exclusively. 3. The additional study of persistence of genotoxicity may identify organs susceptible for carcinogenicity. Presently, we are working on new techniques to detect DNA SSB and other events with microscale methods. This is necessary to allow a more complete elucidation of genotoxicity in remote target organs and with other carcinogens which may not induce DNA SSB. Accordingly in the near future we expect to have even more versatile tools available to study toxicokinetics of foreign compound. Meanwhile our work with N-nitrosamines is continuing in order to better understand their in vivo modes of action and to better evaluate their burden and risk for man.
摘要
  1. 体外研究表明,器官特异性代谢活化似乎对所研究亚硝胺的体内活性不起主要作用。2. 用亚硝胺对大鼠进行1小时暴露后的体内研究,可以区分对遗传毒性敏感的器官和不敏感的器官。致癌性研究中的非靶器官不能仅靠这种方法来确定。3. 对遗传毒性持久性的进一步研究可能会确定对致癌性敏感的器官。目前,我们正在致力于开发新技术,用微尺度方法检测DNA单链断裂和其他事件。这对于更全面地阐明远程靶器官中的遗传毒性以及其他可能不会诱导DNA单链断裂的致癌物的遗传毒性是必要的。因此,在不久的将来,我们期望有更多通用的工具来研究外来化合物的毒代动力学。同时,我们对N-亚硝胺的研究仍在继续,以便更好地了解它们的体内作用模式,并更好地评估它们对人类的负担和风险。

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