Cytochronne b(5) and epoxide hydrolase contribute to benzo[a]pyrene-DNA adduct formation catalyzed by cytochrome P450 1A1 under low NADPH:P450 oxidoreductase conditions

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F14%3A10282782" target="_blank" >RIV/00216208:11310/14:10282782 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1016/j.tox.2014.02.002" target="_blank" >http://dx.doi.org/10.1016/j.tox.2014.02.002</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.tox.2014.02.002" target="_blank" >10.1016/j.tox.2014.02.002</a>

Result language
angličtina
Original language name
Cytochronne b(5) and epoxide hydrolase contribute to benzo[a]pyrene-DNA adduct formation catalyzed by cytochrome P450 1A1 under low NADPH:P450 oxidoreductase conditions
Original language description
In previous studies we had administered benzo[a]pyrene (BaP) to genetically engineered mice (HRN) which do not express NADPH:cytochrome P450 oxidoreductase (POR) in hepatocytes and observed higher DNA adduct levels in livers of these mice than in wild-type mice. To elucidate the reason for this unexpected finding we have used two different settings for in vitro incubations; hepatic microsomes from control and BaP-pretreated HRN mice and reconstituted systems with cytochrome P450 1A1 (CYP1A1), POR, cytochrome b(5), and epoxide hydrolase (mEH) in different ratios. In microsomes from BaP-pretreated mice, in which Cyp1a1 was induced, higher levels of BaP metabolites were formed, mainly of BaP-7,8-dihydrodiol. At a low POR:CYP1A1 ratio of 0.05:1 in the reconstituted system, the amounts of BaP diones and BaP-9-ol formed were essentially the same as at an equimolar ratio, but formation of BaP-3-ol was similar to 1.6-fold higher. Only after addition of mEH were BaP dihydrodiols found. Two BaP-
Czech name
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Czech description
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Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
CE - Biochemistry
OECD FORD branch
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Project
<a href="/en/project/GAP301%2F10%2F0356" target="_blank" >GAP301/10/0356: Study of contribution of different DNA-damaging mechanisms to toxicity of cytostatics to human chemosensitive and chemoresistant neuroblastomas</a><br>
Continuities
S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2014
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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