Department of Epigenetics, Van Andel Institute, Grand Rapids, MI, United States.
Department of Epigenetics, Van Andel Institute, Grand Rapids, MI, United States; Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, United States.
Adv Pharmacol. 2023;96:319-365. doi: 10.1016/bs.apha.2022.08.004. Epub 2022 Oct 26.
Arsenic is a naturally occurring metal carcinogen found in the Earth's crust. Millions of people worldwide are chronically exposed to arsenic through drinking water and food. Exposure to inorganic arsenic has been implicated in many diseases ranging from acute toxicities to malignant transformations. Despite the well-known deleterious health effects of arsenic exposure, the molecular mechanisms in arsenic-mediated carcinogenesis are not fully understood. Since arsenic is non-mutagenic, the mechanism by which arsenic causes carcinogenesis is via alterations in epigenetic-regulated gene expression. There are two possible ways by which arsenic may modify the epigenome-indirectly through an arsenic-induced generation of reactive oxygen species which then impacts chromatin remodelers, or directly through interaction and modulation of chromatin remodelers. Whether directly or indirectly, arsenic modulates epigenetic gene regulation and our understanding of the direct effect of this modulation on chromatin structure is limited. In this chapter we will discuss the various ways by which inorganic arsenic affects the epigenome with consequences in health and disease.
砷是一种存在于地壳中的天然金属致癌物。全世界数百万人通过饮用水和食物慢性接触砷。无机砷暴露与许多疾病有关，从急性毒性到恶性转化。尽管砷暴露对健康的有害影响众所周知，但砷介导的致癌作用的分子机制尚不完全清楚。由于砷是非致突变的，因此砷致癌的机制是通过改变表观遗传调控的基因表达。砷可能通过两种方式改变表观基因组——间接通过砷诱导的活性氧产生，从而影响染色质重塑剂，或直接通过与染色质重塑剂相互作用和调节。无论是直接还是间接的，砷都会调节表观遗传基因调控，我们对这种调节对染色质结构的直接影响的理解是有限的。在本章中，我们将讨论无机砷影响表观基因组的各种方式，以及这些方式在健康和疾病中的后果。
