Department of Biophysics of Environmental Pollution, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska Str. 141/143, 90-236 Lodz, Poland.
Int J Mol Sci. 2021 Dec 15;22(24):13453. doi: 10.3390/ijms222413453.
Epigenetic changes constitute one of the processes that is involved in the mechanisms of carcinogenicity. They include dysregulation of DNA methylation processes, disruption of post-translational patterns of histone modifications, and changes in the composition and/or organization of chromatin. Benzo(a)pyrene (BaP) influences DNA methylation and, depending on its concentrations, as well as the type of cell, tissue and organism it causes hypomethylation or hypermethylation. Moreover, the exposure to polyaromatic hydrocarbons (PAHs), including BaP in tobacco smoke results in an altered methylation status of the offsprings. Researches have indicated a potential relationship between toxicity of BaP and deregulation of the biotin homeostasis pathway that plays an important role in the process of carcinogenesis. Animal studies have shown that parental-induced BaP toxicity can be passed on to the F1 generation as studied on marine medaka (), and the underlying mechanism is likely related to a disturbance in the circadian rhythm. In addition, ancestral exposure of fish to BaP may cause intergenerational osteotoxicity in non-exposed F3 offsprings. Epidemiological studies of lung cancer have indicated that exposure to BaP is associated with changes in methylation levels at 15 CpG; therefore, changes in DNA methylation may be considered as potential mediators of BaP-induced lung cancer. The mechanism of epigenetic changes induced by BaP are mainly due to the formation of CpG-BPDE adducts, between metabolite of BaP-BPDE and CpG, which leads to changes in the level of 5-methylcytosine. BaP also acts through inhibition of DNA methyltransferases activity, as well as by increasing histone deacetylases HDACs, i.e., HDAC2 and HDAC3 activity. The aim of this review is to discuss the mechanism of the epigenetic action of BaP on the basis of the latest publications.
表观遗传改变是致癌机制的一个过程。它们包括 DNA 甲基化过程的失调、组蛋白修饰的翻译后模式的破坏，以及染色质的组成和/或组织的改变。苯并[a]芘 (BaP) 影响 DNA 甲基化，并且取决于其浓度、细胞类型、组织和生物体，它会导致低甲基化或高甲基化。此外，暴露于多环芳烃 (PAHs)，包括烟草烟雾中的 BaP，会导致后代的甲基化状态发生改变。研究表明，BaP 的毒性与其生物素动态平衡途径的失调之间存在潜在的关系，该途径在致癌过程中起着重要作用。动物研究表明，父母诱导的 BaP 毒性可以传递给 F1 代，就像在海洋 medaka（）上进行的研究一样，其潜在机制可能与昼夜节律紊乱有关。此外，鱼类祖先暴露于 BaP 可能会导致未暴露的 F3 后代发生代际骨毒性。肺癌的流行病学研究表明，暴露于 BaP 与 15 个 CpG 甲基化水平的变化有关；因此，DNA 甲基化的变化可能被认为是 BaP 诱导肺癌的潜在介质。BaP 诱导的表观遗传变化的机制主要是由于 BaP 代谢物 BPDE 与 CpG 之间形成了 CpG-BPDE 加合物，导致 5-甲基胞嘧啶水平发生变化。BaP 还通过抑制 DNA 甲基转移酶的活性以及增加组蛋白去乙酰化酶 HDACs（即 HDAC2 和 HDAC3）的活性来发挥作用。本综述的目的是根据最新的出版物讨论 BaP 对 DNA 甲基化的表观遗传作用机制。
