The relationship between DNA adduct formation by benzo[a]pyrene and expression of its activation enzyme cytochrome P450 1A1 in rat
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
14329
Cancer Research UK - United Kingdom
PubMed
24095716
DOI
10.1016/j.etap.2013.09.004
PII: S1382-6689(13)00196-8
Knihovny.cz E-resources
- Keywords
- (32)P-postlabeling, 10-(deoxyguanosin-N(2)-yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene, 5-bromo-4-chloro-3′-indolyphosphate p-toluidine salt, 7-ethoxyresorufin O-deethylation, 7-methoxyresorufin O-deethylation, AHR, BCIP, BNF, BPDE, BaP, BaP-7,8-dihydrodiol-9,10-epoxide, Benzo[a]pyrene, CYP, Cytochrome P450 1A1/2, DMSO, DNA adducts, EROD, Induction, MROD, Metabolic Activation and Detoxification, NBT, PAH, RAL, SDS, TLC, aryl hydrocarbon receptor, benzo[a]pyrene, cytochrome P450, dG-N(2)-BPDE, dimethyl sulfoxide, mEH, microsomal epoxide hydrolase, nitro-blue tetrazolium chloride, polycyclic aromatic hydrocarbon, relative adduct labeling, sodium dodecyl sulfate, thin-layer chromatography, β-naphthoflavone,
- MeSH
- DNA Adducts metabolism MeSH
- Enzyme Activation drug effects MeSH
- Benzo(a)pyrene toxicity MeSH
- beta-Naphthoflavone pharmacology MeSH
- Chromatography, Thin Layer MeSH
- Cytochrome P-450 CYP1A1 metabolism MeSH
- Cytochrome P-450 CYP1A2 biosynthesis genetics MeSH
- Isoenzymes drug effects metabolism MeSH
- Microsomes, Liver drug effects enzymology metabolism MeSH
- Liver drug effects enzymology metabolism MeSH
- Rats MeSH
- Environmental Pollutants toxicity MeSH
- Rats, Wistar MeSH
- Intestine, Small drug effects enzymology metabolism MeSH
- Blotting, Western MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- DNA Adducts MeSH
- Benzo(a)pyrene MeSH
- beta-Naphthoflavone MeSH
- Cytochrome P-450 CYP1A1 MeSH
- Cytochrome P-450 CYP1A2 MeSH
- Isoenzymes MeSH
- Environmental Pollutants MeSH
Benzo[a]pyrene (BaP) is a human carcinogen requiring metabolic activation prior to reaction with DNA. Cytochrome P450 (CYP) 1A1 is the most important hepatic and intestinal enzyme in both BaP activation and detoxification. CYP1A2 is also capable of oxidizing BaP, but to a lesser extent. The induction of CYP1A1/2 by BaP and/or β-naphthoflavone in liver and small intestine of rats was investigated. Both BaP and β-naphthoflavone induced CYP1A expression and increased enzyme activities in both organs. Moreover, the induction of CYP1A enzyme activities resulted in an increase in formation of BaP-DNA adducts detected by (32)P-postlabeling in rat liver and in the distal part of small intestine in vivo. The increases in CYP1A enzyme activity were also associated with bioactivation of BaP and elevated BaP-DNA adduct levels in ex vivo incubations of microsomes of both organs with DNA and BaP. These findings indicate a stimulating effect of both compounds on BaP-induced carcinogenesis.
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