Department of Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, India.
School of Medical Science & Technology, Indian Institute of Technology, Kharagpur, India.
Sci Total Environ. 2019 Mar 15;656:760-777. doi: 10.1016/j.scitotenv.2018.11.381. Epub 2018 Nov 28.
Air pollution is one of the leading causes of deaths in Southeast Asian countries including India. Exposure to air pollutants affects vital cellular mechanisms and is intimately linked with the etiology of a number of chronic diseases. Earlier work from our laboratory has shown that airborne particulate matter disturbs the mitochondrial machinery and causes significant damage to the epigenome. Mitochondrial reactive oxygen species possess the ability to trigger redox-sensitive signaling mechanisms and induce irreversible epigenomic changes. The electrophilic nature of reactive metabolites can directly result in deprotonation of cytosine at C-5 position or interfere with the DNA methyltransferases activity to cause alterations in DNA methylation. In addition, it also perturbs level of cellular metabolites critically involved in different epigenetic processes like acetylation and methylation of histone code and DNA hypo or hypermethylation. Interestingly, these modifications may persist through downstream generations and result in the transgenerational epigenomic inheritance. This phenomenon of subsequent transfer of epigenetic modifications is mainly associated with the germ cells and relies on the germline stability of the epigenetic states. Overall, the recent literature supports, and arguably strengthens, the contention that air pollution might contribute to transmission of epimutations from gametes to zygotes by involving mitochondrial DNA, parental allele imprinting, histone withholding and non-coding RNAs. However, larger prospective studies using innovative, integrated epigenome-wide metabolomic strategy are highly warranted to assess the air pollution induced transgenerational epigenetic inheritance and associated human health effects.
空气污染是包括印度在内的东南亚国家主要的死亡原因之一。暴露于空气污染物会影响重要的细胞机制，并与许多慢性疾病的病因密切相关。我们实验室的早期工作表明，空气中的颗粒物会干扰线粒体机制，并对表观基因组造成重大损害。线粒体活性氧具有触发氧化还原敏感信号机制的能力，并诱导不可逆的表观基因组变化。反应性代谢物的亲电性可直接导致胞嘧啶在 C-5 位置脱质子化，或干扰 DNA 甲基转移酶的活性，导致 DNA 甲基化的改变。此外，它还会扰乱细胞代谢物的水平，这些代谢物与不同的表观遗传过程密切相关，如组蛋白密码的乙酰化和甲基化以及 DNA 低甲基化或高甲基化。有趣的是，这些修饰可能会通过下游世代持续存在，并导致跨代表观基因组遗传。这种后续表观遗传修饰转移的现象主要与生殖细胞有关，并依赖于表观遗传状态的种系稳定性。总的来说，最近的文献支持并可以说加强了这样一种观点，即空气污染可能通过涉及线粒体 DNA、亲本等位基因印迹、组蛋白保留和非编码 RNA 从配子向合子传递表观突变。然而，使用创新的、综合的全基因组代谢组学策略进行更大规模的前瞻性研究，对于评估空气污染引起的跨代表观遗传遗传及其相关的人类健康影响是非常必要的。
