砷是一种强致癌物，并在全球范围内引起了重大的健康问题。人体摄入饮用水和受污染食物，以及吸入污染物均可能导致砷暴露。流行病学证据表明，砷可导致皮肤、肺、肝脏和膀胱等组织的癌症。尽管动物和细胞培养模型的研究支持砷是一种致癌物，但砷致癌机制尚不完全了解。由于其代谢能力和针对细胞中许多细胞通路的能力，砷致癌是一个复杂的过程。砷代谢和多种形式的砷在其毒性和对致癌终点的贡献方面发挥着不同的作用，因此必须予以考虑。砷生成活性氧物种，增加氧化应激，并损伤DNA和其他大分子。同时，砷抑制DNA修复，改变基因表达的表观遗传调控，并通过替换选择性蛋白质中的锌来靶向蛋白质功能。尽管这些机制有助于砷致癌，但对于砷癌的复杂性仍存在重大的认识差距。未来，改进用于砷癌研究的模型和使用砷诱导的人类肿瘤将有助于弥补对砷驱动肿瘤的理解差距。 版权所有© 2023 Elsevier Inc. 保留所有权利。

Arsenic is a potent carcinogen and poses a significant health concern worldwide. Exposure occurs through ingestion of drinking water and contaminated foods and through inhalation due to pollution. Epidemiological evidence shows arsenic induces cancers of the skin, lung, liver, and bladder among other tissues. While studies in animal and cell culture models support arsenic as a carcinogen, the mechanisms of arsenic carcinogenesis are not fully understood. Arsenic carcinogenesis is a complex process due its ability to be metabolized and because of the many cellular pathways it targets in the cell. Arsenic metabolism and the multiple forms of arsenic play distinct roles in its toxicity and contribute differently to carcinogenic endpoints, and thus must be considered. Arsenic generates reactive oxygen species increasing oxidative stress and damaging DNA and other macromolecules. Concurrently, arsenic inhibits DNA repair, modifies epigenetic regulation of gene expression, and targets protein function due its ability to replace zinc in select proteins. While these mechanisms contribute to arsenic carcinogenesis, there remain significant gaps in understanding the complex nature of arsenic cancers. In the future improving models available for arsenic cancer research and the use of arsenic induced human tumors will bridge some of these gaps in understanding arsenic driven cancers.Copyright © 2023 Elsevier Inc. All rights reserved.