Establishing a role for environmental toxicant exposure induced epigenetic remodeling in malignant transformation.
Establishing a role for environmental toxicant exposure induced epigenetic remodeling in malignant transformation.
复制标题
确定环境毒物暴露在恶性转化中诱导表观遗传重塑的作用。
DOI：
10.1016/j.semcancer.2018.11.002
复制
发表时间：
2019
影响因子：
14.5
通讯作者：
Ohm,JoyceE
中科院分区：
文献类型：
--
作者：
Humphrey,KristenM;Pandey,Sumali;Martin,Jeffery;Hagoel,Tamara;Grand'Maison,Anne;Ohm,JoyceE
人类在其一生中暴露于各种各样的环境暴露。其中包括天然存在的毒素和化学毒物，如杀虫剂、除草剂和工业化学品，其中许多物质被认为可能导致人类疾病易感性[[1]、[2]、[3]]。我们和其他人假设，环境暴露可能会导致再生细胞群和发育中的生物体发生适应性表观遗传变化，导致基因表达异常，并增加生命后期的疾病易感性[3]。常见的表观遗传变化包括miRNA表达的变化、共价组蛋白修饰和DNA甲基化。重要的是，由于它们的遗传性质，在干细胞内发生的异常表观遗传修饰可能特别有害。再生细胞系中的异常表观遗传变化可以传递到大量的子细胞中，并且可以持续很长一段时间。众所周知，表观遗传变化的积累可导致许多人类疾病，包括癌症[[4]，[5]，[6]]。因此，我们必须增加对常见环境毒素和毒物如何诱导表观遗传变化的理解，特别是在干细胞群体中。在这篇综述中，我们将讨论美国和世界各地常见的环境暴露如何导致表观遗传变化，并讨论与人类疾病（包括癌症）的潜在联系。
Humans are exposed to a wide variety of environmental exposures throughout their lifespan. These include both naturally occurring toxins and chemical toxicants like pesticides, herbicides, and industrial chemicals, many of which have been implicated as possible contributors to human disease susceptibility [[1], [2], [3]]. We, and others, have hypothesized that environmental exposures may cause adaptive epigenetic changes in regenerative cell populations and developing organisms, leading to abnormal gene expression and increased disease susceptibility later in life [3]. Common epigenetic changes include changes in miRNA expression, covalent histone modifications, and methylation of DNA. Importantly, due to their heritable nature, abnormal epigenetic modifications which occur within stem cells may be particularly deleterious. Abnormal epigenetic changes in regenerative cell linages can be passed onto a large population of daughter cells and can persist for long periods of time. It is well established that an accumulation of epigenetic changes can lead to many human diseases including cancer [[4], [5], [6]]. Subsequently, it is imperative that we increase our understanding of how common environmental toxins and toxicants can induce epigenetic changes, particularly in stem cell populations. In this review, we will discuss how common environmental exposures in the United States and around the world may lead to epigenetic changes and discuss potential links to human disease, including cancer.