Insights into the carcinogenic mode of action of arsenic
Insights into the carcinogenic mode of action of arsenic
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DOI：
10.1016/j.taap.2006.10.006
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发表时间：
2007-08-01
影响因子：
3.8
通讯作者：
Tennant, A. H.
中科院分区：
文献类型：
--
作者：
Kligerman, A. D.;Tennant, A. H.
自世纪晚期以来，人们就知道砷会诱发人类癌症，但砷如何诱发癌症一直是众多科学出版物的主题。人们针对砷的致癌性提出了各种作用模式（MOA）。在本文中，我们回顾了我们以前的研究砷的能力，造成DNA损伤，这些砷的相对不能诱导点突变，砷的参与纺锤体中断。我们提出了新的证据表明，还原型谷胱甘肽（GSH）可以化学还原非活性五价砷三价砷，可以破坏微管蛋白聚合，并表明活性氧（ROS）是最有可能不参与微管蛋白破坏。还提出了一个假说，砷可能会引起稳定的染色体畸变（CA），可导致癌症，从而支持砷的MOA遗传损伤的作用。然后，我们提出了有前途的研究领域，可能会深入了解砷的MOA。爱思唯尔公司出版
That arsenic can induce cancer in humans has been known since the late 17th century, yet how arsenic induces cancer has been the subject of numerous scientific publications. Various modes of action (MOA) have been proposed for arsenic's carcinogenicity. In this paper we review our previous studies on the ability of arsenicals to cause DNA damage, the relative inability of these arsenicals to induce point mutations, and the involvement of arsenicals in spindle disruption. We present new evidence that shows that reduced glutathione (GSH) can chemically reduce inactive pentavalent arsenicals to trivalent arsenicals which can disrupt tubulin polymerization, and show that reactive oxygen species (ROS) are most likely not involved in tubulin disruption. A hypothesis is also presented on how arsenic may induce stable chromosome aberrations (CAs) that can lead to cancer, thus supporting a role for genetic damage in the MOA for arsenic. We then propose promising areas of research that might give insight into the MOA of arsenic. Published by Elsevier Inc.