Influence of Benzo(a)pyrene on Different Epigenetic Processes

Abstract

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 (Oryzias melastigma), 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.

Benzo[a]pyrene—Environmental Occurrence, Human Exposure, and Mechanisms of Toxicity

“…In mammals, B[ a ]P is readily absorbed after inhalation, oral administration, and through the skin [ 4 ]. The main sources of human B[ a ]P exposure are contaminated food and the air [ 5 ].…”

“…B[ a ]P also influences the expression of histones [ 137 , 138 ] and induces the expression of miRNAs [ 139 ]. Bukowska and Sicińska [ 5 ] presented in their review that the mechanism of epigenetic changes induced by B[ a ]P was mainly associated with the creation of CpG-BPDE adducts, between B[ a ]P metabolite—BPDE—and CpG that led to alterations in the level of 5-methylcytosine [ 133 , 134 , 135 ]. Moreover, B[ a ]P has been shown to be able to inhibit the activities of DNA methyltransferases [ 140 , 141 ] and increase the activities of histone deacetylases (HDACs) [ 137 ] ( Figure 8 ).…”

Protective Effect of Thyme and Chestnut Honeys Enriched with Bee Products against Benzo(a)pyrene-Induced DNA Damage

“…According to the International Agency for Research on Cancer (IARC), BaP is a Group I carcinogen to humans [ 19 ]. BaP is also genotoxic, mutagenic, epigenotoxic, teratogenic, and neurotoxic, and it impairs fertility [ 20 , 21 ]. One of BaP’s mechanisms of action is its pro-oxidative effects that lead to lipid peroxidation, protein carbonylation, and DNA damage [ 15 ].…”

Inhibition of RNF182 mediated by Bap promotes non-small cell lung cancer progression

“…Once binding to its ligands, AhR translocates into the nucleus and regulates a battery of gene expression. Activation of AhR is one of the mechanisms responsible for adverse effects of Bap (7)(8)(9)(10)(11).…”