Wang Yewei, Charkoftaki Georgia, Davidson Emily, Orlicky David J, Tanguay Robyn L, Thompson David C, Vasiliou Vasilis, Chen Ying
Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06510, USA.
Department of Cellular & Molecular Physiology, Yale School of Medicine, Yale University, New Haven, CT 06510, USA.
Curr Opin Environ Sci Health. 2022 Oct;29. doi: 10.1016/j.coesh.2022.100389. Epub 2022 Aug 15.
1,4-Dioxane (DX) is an emerging drinking water contaminant worldwide, which poses a threat to public health due to its demonstrated liver carcinogenicity and potential for human exposure. The lack of drinking water standards for DX is attributed to undetermined mechanisms of DX carcinogenicity. This mini-review provides a brief discussion of a series of mechanistic studies, wherein unique mouse models were exposed to DX in drinking water to elucidate redox changes associated with DX cytotoxicity and genotoxicity. The overall conclusions from these studies support a direct genotoxic effect by high dose DX and imply that oxidative stress involving CYP2E1 activation may play a causal role in DX liver genotoxicity and potentially carcinogenicity. The mechanistic data derived from these studies can serve as important references to refine the assessment of carcinogenic pathways that may be triggered at environmentally relevant low doses of DX in future animal and human studies.
1,4-二氧六环（DX）是一种在全球范围内新出现的饮用水污染物，因其已被证实的肝脏致癌性以及对人类的潜在暴露风险，对公众健康构成威胁。缺乏DX的饮用水标准归因于其致癌机制尚未确定。本综述简要讨论了一系列机制研究，其中使用独特的小鼠模型饮用含DX的水，以阐明与DX细胞毒性和遗传毒性相关的氧化还原变化。这些研究的总体结论支持高剂量DX具有直接遗传毒性作用，并暗示涉及CYP2E1激活的氧化应激可能在DX肝脏遗传毒性及潜在致癌性中起因果作用。这些研究得出的机制数据可作为重要参考，以完善未来动物和人体研究中对环境相关低剂量DX可能引发的致癌途径的评估。
