Induction of biotransformation enzymes by the carcinogenic air-pollutant 3-nitrobenzanthrone in liver, kidney and lung, after intra-tracheal instillation in rats
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
Cancer Research UK - United Kingdom
PubMed
21167309
DOI
10.1016/j.mrgentox.2010.12.003
PII: S1383-5718(10)00410-9
Knihovny.cz E-resources
- MeSH
- DNA Adducts MeSH
- Benz(a)Anthracenes metabolism pharmacology MeSH
- Cytochrome P-450 CYP1A1 metabolism MeSH
- Cytochrome P-450 CYP1A2 metabolism MeSH
- Cytosol drug effects MeSH
- Enzyme Induction drug effects MeSH
- Liver enzymology MeSH
- Carcinogens pharmacology MeSH
- Rats MeSH
- Air Pollutants pharmacology MeSH
- Kidney enzymology MeSH
- Microsomes drug effects MeSH
- NAD(P)H Dehydrogenase (Quinone) metabolism MeSH
- Lung enzymology MeSH
- Rats, Sprague-Dawley MeSH
- Trachea MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 3-aminobenzanthrone MeSH Browser
- 3-nitrobenzanthrone MeSH Browser
- DNA Adducts MeSH
- Benz(a)Anthracenes MeSH
- Cytochrome P-450 CYP1A1 MeSH
- Cytochrome P-450 CYP1A2 MeSH
- Carcinogens MeSH
- Air Pollutants MeSH
- NAD(P)H Dehydrogenase (Quinone) MeSH
- NQO1 protein, human MeSH Browser
3-Nitrobenzanthrone (3-NBA), a carcinogenic air pollutant, was investigated for its ability to induce cytochrome P450 (CYP) 1A1/2 and NAD(P)H:quinone oxidoreductase (NQO1) in liver, kidney and lung of rats treated by intra-tracheal instillation. The organs used were from a previous study performed to determine the persistence of 3-NBA-derived DNA adducts in target and non-target tissues (Bieler et al., Carcinogenesis 28 (2007) 1117-1121, [22]). NQO1 is the enzyme reducing 3-NBA to N-hydroxy-3-aminobenzanthrone (N-OH-3-ABA) and CYP1A enzymes oxidize a human metabolite of 3-NBA, 3-aminobenzanthrone (3-ABA), to yield the same reactive intermediate. 3-NBA and 3-ABA are both activated to species forming DNA adducts by cytosols and/or microsomes isolated from rat lung, the target organ for 3-NBA carcinogenicity, and from liver and kidney. Each compound generated the same five DNA adducts detectable by (32)P-postlabelling. When hepatic cytosols from rats treated with 0.2 or 2mg/kg body weight of 3-NBA were incubated with 3-NBA, DNA adduct formation was 3.2- and 8.6-fold higher, respectively, than in incubations with cytosols from control animals. Likewise, cytosols isolated from lungs and kidneys of rats exposed to 3-NBA more efficiently activated 3-NBA than those of control rats. This increase corresponded to an increase in protein levels and enzymatic activities of NQO1. Incubations of hepatic, pulmonary or renal microsomes of 3-NBA-treated rats with 3-ABA led to an 9.6-fold increase in DNA-adduct formation relative to controls. The highest induction in DNA-adduct levels was found in lung. The stimulation of DNA-adduct formation correlated with expression of CYP1A1/2 induced by the intra-tracheal instillation of 3-NBA. The results demonstrate that 3-NBA induces NQO1 and CYP1A1/2 in livers, lungs and kidneys of rats after intra-tracheal instillation, thereby enhancing its own genotoxic and carcinogenic potential.
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