The relationship between DNA adduct formation by benzo[a]pyrene and expression of its activation enzyme cytochrome P450 1A1 in rat
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
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-zdroje
- Klíčová slova
- (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
- adukty DNA metabolismus MeSH
- aktivace enzymů účinky léků MeSH
- benzopyren toxicita MeSH
- beta-naftoflavon farmakologie MeSH
- chromatografie na tenké vrstvě MeSH
- cytochrom P-450 CYP1A1 metabolismus MeSH
- cytochrom P-450 CYP1A2 biosyntéza genetika MeSH
- izoenzymy účinky léků metabolismus MeSH
- jaterní mikrozomy účinky léků enzymologie metabolismus MeSH
- játra účinky léků enzymologie metabolismus MeSH
- krysa rodu Rattus MeSH
- látky znečišťující životní prostředí toxicita MeSH
- potkani Wistar MeSH
- tenké střevo účinky léků enzymologie metabolismus MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- adukty DNA MeSH
- benzopyren MeSH
- beta-naftoflavon MeSH
- cytochrom P-450 CYP1A1 MeSH
- cytochrom P-450 CYP1A2 MeSH
- izoenzymy MeSH
- látky znečišťující životní prostředí 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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