Diallyl Trisulfide Enhances Benzo[ a]pyrene-induced CYP1A1 Expression and Metabolic Activation in Hepatic HepG2 Cells

Abstract

Background/aim: Benzo[a]pyrene (BaP), an environmental pollutant produced by combustion processes, induces expression of cytochrome P450 (CYP) 1A1 via the activation of aryl hydrocarbon receptor (AHR). Induced CYP1A1 is involved in BaP metabolism, resulting in either detoxification or metabolic activation in a context-dependent manner. The effect of diallyl trisulfide (DATS), a garlic-derived organosulfur compound, on BaP metabolism has not been investigated.

Materials and methods: The combined effect of DATS and BaP on BaP metabolism in hepatocyte-derived HepG2 cells was examined.

Results: DATS enhanced BaP-induced CYP1A1 and CYP1B1 mRNA expression, BaP hydroxylation and BaP-DNA adduct formation. Combined treatment of BaP and DATS also increased reactive oxygen species levels. DATS enhanced BaP-induced AHR recruitment and histone H3 acetylation on the CYP1A1 promoter.

Conclusion: DATS combined treatment enhances BaP metabolic activation through an AHR-modulating mechanism.

Keywords: Benzo[a]pyrene; DNA adduct formation; cytochrome P450 1A1; diallyl trisulfide; histone acetylation.