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Epigenetic regulation of Cytochrome P450 (CYP1A1) by polycyclic aromatic hydrocarbons
Author(s) -
Rosario Olguin Sitlali,
Camacho Rafael,
Espinosa Jesus Javier
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.lb95
Subject(s) - epigenetics , aryl hydrocarbon receptor , gene expression , dna methylation , cytochrome p450 , regulation of gene expression , chemistry , polycyclic aromatic hydrocarbon , methylation , benzo(a)pyrene , gene , microbiology and biotechnology , pyrene , histone , biology , carcinogen , transcription factor , biochemistry , enzyme , environmental chemistry , organic chemistry
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.