J Pharm Pharmacogn Res 2(Suppl. 1): S31, 2014
Special supplement with the abstract book of LATINFARMA 2013
C 015: EFFECT OF DNA DEMETHYLATION ON CYP1A1 GENE EXPRESSION IN RAT CELLS
Olguín-Reyes S, Camacho-Carranza R, Espinosa-Aguirre JJ.Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, UNAM, México D.F.
Gene regulation involves transcription factors, responsive elements, enhancers, insulators, DNA methylation, histone methylation, acetylation, and deacetylation, among others. In a whole organism, such components may depend on external factors such as environmental pollution. Polycyclic aromatic hydrocarbons (PAH) found in environmental pollution, are susceptible of biotransformation by CYP1A1, a phase I enzyme. In turn, CYP1A1 gene expression is induced by PAHs through the aromatic hydrocarbon receptor (AhR).
However, PAHs exposure affects not only CYP1A1 expression through AhR but also may affect other proteins involved in epigenetic regulation. In order to test this hypothesis, rat hepatocytes clone-9 cell line (C9) was exposed to benzo[a]pyrene (BaP) and to the DNMTs inhibitor 5’-Aza-2’-deoxycitidine (5AzadC), with their respective controls. CYP1A1 expression was determined by qPCR and western blot analysis. The concentration of DNMT3a was also determined. CYP1A1 gene expression was increased after BaP treatment and exacerbated when 5AzadC was co-administrated. DNMT3a protein level decrease in C9 culture after 5AzadC as expected. BaP treatment also produces decrease in DNMT3a protein, although not at the same level seen after 5AzadC treatment. We can conclude that the mechanism behind the positive modulation of CYP1A1 by BaP involves not only AhR but other proteins of the epigenetic machinery like DNMT.