Ghosh Pritha, Banerjee Mayukh, Giri Ashok K, Ray Kunal
Molecular & Human Genetics Division, Indian Institute of Chemical Biology, Council of Scientific & Industrial Research, 4 Raja S.C. Mullick Road, Jadavpur, Kolkata 700 032, India.
Mutat Res. 2008 Sep-Oct;659(3):293-301. doi: 10.1016/j.mrrev.2008.06.003. Epub 2008 Jun 27.
Exposure to arsenic, a toxic metalloid distributed widely in nature, has been known to result in hazardous health outcomes including cancer. Incidence of arsenic toxicity, mostly from usage of underground water, has been reported from different corners of the world spanning more than 21 countries. Recent studies have radically influenced our knowledge on the level of toxicity imparted by different chemical forms of the metalloid. To understand the basic biology for arsenic metabolism different species have been studied at the molecular level, which has unraveled a wealth of information. However, there is no ideal animal model that can be used to understand arsenic toxicity in humans prompting the investigators to undertake the study directly in human cell lines and on affected individuals in areas of exposure. It is interesting to note that only a subset of exposed individuals demonstrate pathological features, i.e. skin lesions sometimes followed by cancer. Also, the extent of affectedness varies remarkably between individuals exposed to similar levels of arsenic. These observations led to investigation of genomic variation in exposed individuals as a potential contributing factor for differential susceptibility. An impressive number of studies have been published on variation in global gene expression and the potential association of candidate genes with arsenic-induced pathology. While there are excellent reviews relating to arsenic metabolism in general, there is no comprehensive review presenting the studies described in humans related to the metalloid toxicity. Our goal in this article has been to present the current state of research on this area to help formulate strategies for future studies.
接触砷这种在自然界广泛分布的有毒类金属，已知会导致包括癌症在内的有害健康后果。世界各地超过21个国家都报告了砷中毒事件，其中大部分是由于使用地下水所致。最近的研究从根本上影响了我们对这种类金属不同化学形式所产生毒性水平的认识。为了从分子水平了解砷代谢的基本生物学机制，人们对不同物种进行了研究，这揭示了大量信息。然而，目前还没有理想的动物模型可用于了解人类的砷中毒情况，这促使研究人员直接在人类细胞系以及砷暴露地区的受影响个体上开展研究。值得注意的是，只有一部分暴露个体表现出病理特征，即皮肤病变，有时还会发展为癌症。此外，在接触相同水平砷的个体中，受影响程度也存在显著差异。这些观察结果促使人们研究暴露个体的基因组变异，将其作为易感性差异的一个潜在影响因素。关于全球基因表达变异以及候选基因与砷诱导病理之间的潜在关联，已经发表了大量研究。虽然总体上有关于砷代谢的优秀综述，但尚无全面综述介绍在人类中开展的与这种类金属毒性相关的研究。本文的目的是介绍该领域的当前研究现状，以帮助制定未来研究的策略。
