Loading...
Please wait, while we are loading the content...
Similar Documents
The environmental pollutant and carcinogen 3-nitrobenzanthrone induces cytochrome P450 1A1 and NAD(P)H:quinone oxidoreductase in rat lung and kidney, thereby enhancing its own genotoxicity.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Stiborová, Marie Dračínská, Helena Mizerovská, Jana Frei, Eva Schmeiser, Heinz H. Hudeček, Jiří Hodek, Petr Phillips, David H. Arlt, Volker M. |
| Copyright Year | 2008 |
| Abstract | 3-Nitrobenzanthrone (3-NBA) is a carcinogen occurring in diesel exhaust and air pollution. Using the (32)P-postlabelling method, we found that 3-NBA and its human metabolite, 3-aminobenzanthrone (3-ABA), are activated to species forming DNA adducts by cytosols and/or microsomes isolated from rat lung, the target organ for 3-NBA carcinogenicity, and kidney. Each compound generated identical five DNA adducts. We have demonstrated the importance of pulmonary and renal NAD(P)H:quinone oxidoreductase (NQO1) to reduce 3-NBA to species that are further activated by N,O-acetyltransferases and sulfotransferases. Cytochrome P450 (CYP) 1A1 is the essential enzyme for oxidative activation of 3-ABA in microsomes of both organs, while cyclooxygenase plays a minor role. 3-NBA was also investigated for its ability to induce NQO1 and CYP1A1 in lungs and kidneys, and for the influence of such induction on DNA adduct formation by 3-NBA and 3-ABA. When cytosols from rats treated i.p. with 40mg/kg bw of 3-NBA were incubated with 3-NBA, DNA adduct formation was up to 2.1-fold higher than in incubations with cytosols from control animals. This increase corresponded to an increase in protein level and enzymatic activity of NQO1. Incubations of 3-ABA with microsomes of 3-NBA-treated rats led to up to a fivefold increase in DNA adduct formation relative to controls. The stimulation of DNA adduct formation correlated with the potential of 3-NBA to induce protein expression and activity of CYP1A1. These results demonstrate that 3-NBA is capable to induce NQO1 and CYP1A1 in lungs and kidney of rats thereby enhancing its own genotoxic and carcinogenic potential. |
| Starting Page | 11 |
| Ending Page | 22 |
| Page Count | 12 |
| File Format | PDF HTM / HTML |
| DOI | 10.1016/j.tox.2008.01.018 |
| PubMed reference number | 18329153 |
| Journal | Medline |
| Volume Number | 247 |
| Issue Number | 1 |
| Alternate Webpage(s) | https://kclpure.kcl.ac.uk/portal/files/6248673/Stiborova_2008_Toxicology.pdf |
| Journal | Toxicology |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
