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.
Highlights
BaP acts through inhibition of DNA methyltransferases activity, as well as by increasing histone deacetylases H3inand deacetylases (HDACs), i.e., HDAC2 and HDAC3 activity
BaP is usually determined in high concentration in polyaromatic hydrocarbons (PAHs) mixtures, to which tobacco smokers and workers employed in various industries are exposed
The results showed that genes characterized by methylation changes were identified in children whose mothers smoked during pregnancy
Summary
Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) and is used as an indicator of PAHs. It has been proven that food, drinking water and the air are the prevalent sources of human exposure to. The main mechanisms of action of BaP involve: (1) creation of stable and depurinating DNA adducts, (2) repetitive redox cycling, which generates reactive oxygen species, (3) activation of the aryl hydrocarbon receptor (AhR), (4) immunosuppression and (5) different epigenetic. The epigenetic effect of BaP has been demonstrated in in vitro changes [14]. The epigenetic effect of BaP has been demonstrated in in vitro and in vivo, and in vivo, as well as in epidemiological studies. The ability of carcinogens to disturb as well as in epidemiological studies. The ability of carcinogens to disturb epigenetic epigenetic processes is one of the causes of cancer development. Processes is one of the causes of cancer development
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