Arsenic: health effects, mechanisms of actions, and research issues.
Arsenic: health effects, mechanisms of actions, and research issues.
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DOI：
10.1289/ehp.99107593
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发表时间：
1999-07
影响因子：
10.4
通讯作者：
Waalkes M
中科院分区：
文献类型：
--
作者：
Abernathy CO;Liu YP;Longfellow D;Aposhian HV;Beck B;Fowler B;Goyer R;Menzer R;Rossman T;Thompson C;Waalkes M
1997年9月22日至24日，在马里兰州猎人谷举行了一次关于砷对健康的影响、其作用模式和需要进一步研究的领域的会议。接触饮用水中的砷与皮肤癌和内癌的发生以及糖尿病、周围神经病变和心血管疾病等非致癌效应有关。关于AS的具体作用机制(S)的数据很少，但关于可能的作用模式的信息却很多。虽然亚砷酸盐[As(III)]可以抑制200多种酶，但As诱导非致癌作用的基础事件尚不清楚。在致癌性方面，AS可影响DNA修复、DNA甲基化、增加原癌基因c-myc的自由基形成和激活，但这些潜在途径都没有被广泛接受为主要病因事件。此外，还没有公认的模型来研究砷的致癌作用。在最后一次会议上，我们考虑了研究需要。列举的最重要领域包括：a)砷的代谢及其与细胞成分的相互作用；b)砷的可能生物积累；c)与其他金属的相互作用；d)砷对遗传物质的影响；e)研究砷的影响的动物模型和细胞系统的发展；以及f)更好地描述与健康风险有关的人类暴露的特征。促进AS研究的一些障碍包括：美国对AS研究明显缺乏兴趣；缺乏相关的动物模型；难以采用统一的方法；缺乏公认的生物标志物；以及需要一个储存标本的中央储存库。
A meeting on the health effects of arsenic (As), its modes of action, and areas in need of future research was held in Hunt Valley, Maryland, on 22-24 September 1997. Exposure to As in drinking water has been associated with the development of skin and internal cancers and noncarcinogenic effects such as diabetes, peripheral neuropathy, and cardiovascular diseases. There is little data on specific mechanism(s) of action for As, but a great deal of information on possible modes of action. Although arsenite [As(III)] can inhibit more than 200 enzymes, events underlying the induction of the noncarcinogenic effects of As are not understood. With respect to carcinogenicity, As can affect DNA repair, methylation of DNA, and increase radical formation and activation of the protooncogene c-myc, but none of these potential pathways have widespread acceptance as the principal etiologic event. In addition, there are no accepted models for the study of As-induced carcinogenesis. At the final meeting session we considered research needs. Among the most important areas cited were a) As metabolism and its interaction with cellular constituents; b) possible bioaccumulation of As; c) interactions with other metals; d) effects of As on genetic material; e) development of animal models and cell systems to study effects of As; and f) a better characterization of human exposures as related to health risks. Some of the barriers to the advancement of As research included an apparent lack of interest in the United States on As research; lack of relevant animal models; difficulty with adoption of uniform methodologies; lack of accepted biomarkers; and the need for a central storage repository for stored specimens.