Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
Curriculum in Toxicology, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
Curr Environ Health Rep. 2018 Mar;5(1):134-144. doi: 10.1007/s40572-018-0184-1.
Exposure to inorganic arsenic (iAs) via drinking water represents a significant global public health threat with chronic exposure associated with cancer, skin lesions, neurological impairment, and cardiovascular diseases. Particularly susceptible populations include the developing fetus and young children. This review summarizes some of the critical studies of the long-term health effects and underlying biological mechanisms related to developmental exposure to arsenic. It also highlights the complex factors, such as the sex of the exposed individual, that contribute to susceptibility to the later life health effects of iAs.
Studies in animal models, as well as human population-based studies, have established that prenatal and early life iAs exposures are associated with long-term effects, and many of these effects display sexually dimorphic responses. As an underlying molecular basis, recent epidemiologic and toxicologic studies have demonstrated that changes to the epigenome may play a key mechanistic role underlying many of the iAs-associated health outcomes. Developmental exposure to iAs results in early and later life health effects. Mechanisms underlying these outcomes are likely complex, and include disrupted key biological pathways with ties to the epigenome. This highlights the importance of continued research, particularly in animal models, to elucidate the important underpinnings (e.g., timing of exposure, metabolism, dose) of these complex health outcomes and to identify the biological mechanisms underlying sexual dimorphism in iAs-associated diseases. Future research should investigate preventative strategies for the protection from the detrimental health endpoints associated with early life exposure to iAs. Such strategies could include potential interventions focused on dietary supplementation for example the adoption of a folate-rich diet.
通过饮用水接触无机砷 (iAs) 对全球公共健康构成重大威胁，慢性接触与癌症、皮肤损伤、神经损伤和心血管疾病有关。特别易受影响的人群包括发育中的胎儿和幼儿。本综述总结了一些与砷暴露相关的长期健康影响和潜在生物学机制的关键研究。它还强调了一些复杂的因素，如暴露个体的性别，这些因素导致了对 iAs 后期生活健康影响的易感性。
动物模型研究以及基于人群的研究表明，产前和生命早期 iAs 暴露与长期影响有关，其中许多影响表现出性别二态性反应。作为潜在的分子基础，最近的流行病学和毒理学研究表明，表观基因组的改变可能在许多 iAs 相关健康结果的发生机制中发挥关键作用。iAs 的发育暴露会导致生命早期和后期的健康影响。这些结果的潜在机制可能很复杂，包括与表观基因组有关的关键生物途径的中断。这凸显了继续研究的重要性，特别是在动物模型中，以阐明这些复杂健康结果的重要基础（例如，暴露时间、代谢、剂量），并确定 iAs 相关疾病性别二态性的生物学机制。未来的研究应该调查针对生命早期暴露于 iAs 相关有害健康终点的预防策略。这些策略可能包括针对饮食补充的潜在干预措施，例如采用富含叶酸的饮食。
