Most cited article - PubMed ID 25658126
Enzymes oxidizing the azo dye 1-phenylazo-2-naphthol (Sudan I) and their contribution to its genotoxicity and carcinogenicity
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.
- Keywords
- DNA-adducts, Sudan I, benzo[a]pyrene, cytochromes P450 1A1 and 1A2 and 1B1, genotoxicity, microsomal epoxide hydrolase,
- MeSH
- DNA Adducts toxicity MeSH
- Coloring Agents toxicity MeSH
- Benzo(a)pyrene toxicity MeSH
- Cytochrome P-450 CYP1A1 metabolism MeSH
- Microsomes, Liver drug effects MeSH
- Liver drug effects MeSH
- Carcinogens, Environmental toxicity MeSH
- Rats MeSH
- Naphthols toxicity MeSH
- Rats, Wistar MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- 1-phenylazo-2-naphthol MeSH Browser
- DNA Adducts MeSH
- Coloring Agents MeSH
- benzo(a)pyrene-DNA adduct MeSH Browser
- Benzo(a)pyrene MeSH
- Cytochrome P-450 CYP1A1 MeSH
- Carcinogens, Environmental MeSH
- Naphthols MeSH