Arsenic Exposure and Toxicology: A Historical Perspective
Arsenic Exposure and Toxicology: A Historical Perspective
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DOI：
10.1093/toxsci/kfr184
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发表时间：
2011-10-01
影响因子：
3.8
通讯作者：
Thomas, David J.
中科院分区：
文献类型：
--
作者：
Hughes, Michael F.;Beck, Barbara D.;Thomas, David J.
类金属砷是一种天然的环境污染物，人类经常通过食物、水、空气和土壤接触到砷。砷作为一种杀人剂有着悠久的历史，但在过去的100年里，砷被用作杀虫剂、化学治疗剂和消费品的成分。在世界上的一些地区，饮用水中自然含有高含量的砷，这是一个毒理学问题。砷有几种结构形式和氧化态，因为它与金属形成合金，并与氢、氧、碳和其他元素形成共价键。与环境相关的砷形式是无机和有机的，以三价或五价形式存在。砷的代谢由砷（+3氧化态）甲基转移酶催化，是一个从五价到三价再氧化甲基化回五价的连续过程。三价砷通常比五价砷的毒性更强。砷的急性反应从胃肠不适到死亡。根据剂量的不同，慢性砷暴露可能影响几个主要器官系统。摄入砷的一个主要问题是致癌，主要是皮肤癌、膀胱癌和肺癌。砷对其疾病终点的作用方式目前正在研究中。两个关键领域是三价砷与蛋白质中硫的相互作用以及砷产生氧化应激的能力。随着技术的进步和砷致癌性动物模型的发展，对砷毒理学的认识将不断提高。
The metalloid arsenic is a natural environmental contaminant to which humans are routinely exposed in food, water, air, and soil. Arsenic has a long history of use as a homicidal agent, but in the past 100 years arsenic, has been used as a pesticide, a chemotherapeutic agent and a constituent of consumer products. In some areas of the world, high levels of arsenic are naturally present in drinking water and are a toxicological concern. There are several structural forms and oxidation states of arsenic because it forms alloys with metals and covalent bonds with hydrogen, oxygen, carbon, and other elements. Environmentally relevant forms of arsenic are inorganic and organic existing in the trivalent or pentavalent state. Metabolism of arsenic, catalyzed by arsenic (+3 oxidation state) methyltransferase, is a sequential process of reduction from pentavalency to trivalency followed by oxidative methylation back to pentavalency. Trivalent arsenic is generally more toxicologically potent than pentavalent arsenic. Acute effects of arsenic range from gastrointestinal distress to death. Depending on the dose, chronic arsenic exposure may affect several major organ systems. A major concern of ingested arsenic is cancer, primarily of skin, bladder, and lung. The mode of action of arsenic for its disease endpoints is currently under study. Two key areas are the interaction of trivalent arsenicals with sulfur in proteins and the ability of arsenic to generate oxidative stress. With advances in technology and the recent development of animal models for arsenic carcinogenicity, understanding of the toxicology of arsenic will continue to improve.