Epigenetic regulation of Cytochrome P450 (CYP1A1) by polycyclic aromatic hydrocarbons

Abstract

Gene regulation involves transcription factors, responsive elements, enhancers, insulators, DNA methylation, histone methylation, acetylation, and deacetylation, among others. In an organism, such components might depend on external factors such as environmental pollution. CYP1A1 gene is inducible by polycyclic aromatic hydrocarbon (PAH) through the aromatic hydrocarbon receptor (AhR). However, exposure to PAHs may affect proteins involved in epigenetic regulation, as well as, CYP1A1 epigenetic regulation. In order to probe this, rat hepatocytes clone‐9 cell line (C9) was exposed to benzo[a]pyrene (BaP), benzofluorene (BF), 2’‐7’‐dimethylbenzantracene (DMBA), 3‐methylcholanthrene (3MC) and DNMTs inhibitor 5’‐Aza‐2’‐deoxycitidine (5AzadC).CYP1A1 gene expression was determined by qPCR and DNMT3a protein level by western blot, showing in both cases an increased with all treatments. However, this effect is exacerbated with a PAH‐AzadC treatment, especially with DMBA. Additionally, treatments also increase DNMT3a protein level in C9 culture. In respect to the positive modulation of CYP1A1 gene expression, we suggest that PAHs do not affect CYP1A1 gene expression only through AhR, but it is also affected by its epigenetic regulation.

Persistent DNA methylation changes associated with prenatal NO2exposure in a Canadian prospective birth study

“…The underlying mechanisms of prenatal air pollution exposure include increased oxidative stress and inflammatory signalling and the hypothesized biological embedding of these events in DNAm may contribute to atopic disease in childhood 48 . To investigate this notion, we examined prenatal and postnatal-specific DNAm changes associated with prenatal and year one NO2 exposure, respectively, across a list of 59 a priori-determined candidate genes hypothesized to participate in the cellular pathways activated by air pollution exposure or that were previously identified in epigenome-wide association studies of prenatal air pollution (Supplementary Table 1) 8,9,[49][50][51][52][53][53][54][55][56][57][58][59][59][60][61][62][63][64][65][66] . We also examined whether two previously identified DNAm changes within the genes LONP1 and SLC25A2 could be replicated in our analysis 8 .…”