Benzo[a]pyrene-Induced Genotoxicity in Rats Is Affected by Co-Exposure to Sudan I by Altering the Expression of Biotransformation Enzymes

Abstract

The environmental pollutant benzo[a]pyrene (BaP) is a human carcinogen that reacts with DNA after metabolic activation catalysed by cytochromes P450 (CYP) 1A1 and 1B1 together with microsomal epoxide hydrolase. The azo dye Sudan I is a potent inducer of CYP1A1/2. Here, Wistar rats were either treated with single doses of BaP (150 mg/kg bw) or Sudan I (50 mg/kg bw) alone or with both compounds in combination to explore BaP-derived DNA adduct formation in vivo. Using 32P-postlabelling, DNA adducts generated by BaP-7,8-dihydrodiol-9,10-epoxide were found in livers of rats treated with BaP alone or co-exposed to Sudan I. During co-exposure to Sudan I prior to BaP treatment, BaP-DNA adduct levels increased 2.1-fold in comparison to BaP treatment alone. Similarly, hepatic microsomes isolated from rats exposed to Sudan I prior to BaP treatment were also the most effective in generating DNA adducts in vitro with the activated metabolites BaP-7,8-dihydrodiol or BaP-9-ol as intermediates. DNA adduct formation correlated with changes in the expression and/or enzyme activities of CYP1A1, 1A2 and 1B1 in hepatic microsomes. Thus, BaP genotoxicity in rats in vivo appears to be related to the enhanced expression and/or activity of hepatic CYP1A1/2 and 1B1 caused by exposure of rats to the studied compounds. Our results indicate that the industrially employed azo dye Sudan I potentiates the genotoxicity of the human carcinogen BaP, and exposure to both substances at the same time seems to be hazardous to humans.

Induction by Phenobarbital of Phase I and II Xenobiotic-Metabolizing Enzymes in Bovine Liver: An Overall Catalytic and Immunochemical Characterization

“…Mammalian EHs consist of five members, but only two of them are of ultimate significance; i.e., the microsomal EH (EPHX1) and the soluble EH (EPHX2) [ 163 , 170 ]. Human EPHX1 is responsible for the metabolism of xenobiotic epoxides [ 163 ]; e.g., the aflatoxin B1 exo-8,9-epoxide detoxification and the metabolic activation (together with CYP1A1) of the human carcinogen benzo[ a ]pyrene [ 171 , 172 ]. Despite being involved in xenobiotic epoxide metabolism, EPHX2 mostly metabolizes epoxides derived from fatty acids [ 163 ].…”

Polymorphism of TP53 (rs1042522) gene and peculiarities of the immune profile in children exposed to airborne benzo(a)pyrene

“…Mutagenic and carcinogenic effects of benzo(a)pyrene occur due to covalent linking of its metabolite BaP-7,8-dihydrodiol-9,10-epoxide (BPDE) to nucleotide bases and the subsequent formation of cys-and trans-DNA adducts. This damages a nucleotide sequence, breaks DNA repair and replication and cell transformation and, consequently, results in cell death and / or carcinogenesis [11,12].…”