NADPH- and NADH-dependent metabolism of and DNA adduct formation by benzo[a]pyrene catalyzed with rat hepatic microsomes and cytochrome P450 1A1
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F16%3A10323482" target="_blank" >RIV/00216208:11310/16:10323482 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1007/s00706-016-1713-y" target="_blank" >http://dx.doi.org/10.1007/s00706-016-1713-y</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1007/s00706-016-1713-y" target="_blank" >10.1007/s00706-016-1713-y</a>
Alternative languages
Result language
angličtina
Original language name
NADPH- and NADH-dependent metabolism of and DNA adduct formation by benzo[a]pyrene catalyzed with rat hepatic microsomes and cytochrome P450 1A1
Original language description
Benzo[a]pyrene (BaP) is a human carcinogen that covalently binds to DNA after metabolic activation by cytochrome P450 (CYP) enzymes. Here we investigated the efficiencies of rat hepatic microsomes and rat recombinant CYP1A1 expressed with its reductase, NADPH:CYP oxidoreductase (POR), NADH:cytochrome b (5) reductase, epoxide hydrolase and/or cytochrome b (5) in Supersomes (TM) to metabolize this carcinogen. We also studied the effectiveness of coenzymes of two of the microsomal reductases, NADPH as a coenzyme of POR, and NADH as a coenzyme of NADH:cytochrome b (5) reductase, to mediate BaP metabolism in these systems. Up to eight BaP metabolites and two DNA adducts were generated by the systems, both in the presence of NADPH and NADH. Among BaP metabolites, BaP-9,10-dihydrodiol, BaP-4,5-dihydrodiol, BaP-7,8-dihydrodiol, BaP-1,6-dione, BaP-3,6-dione, BaP-9-ol, BaP-3-ol, and a metabolite of unknown structure were formed by hepatic microsomes and rat CYP1A1. One of two DNA adducts formed by examined enzymatic systems (rat hepatic microsomes and rat CYP1A1) was characterized to be 10-(deoxyguanosin-N (2)-yl)-7,8,9-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (dG-N (2)-BPDE), while another adduct has similar chromatographic properties on polyethylaneimine-cellulose thin layer chromatography to a guanine adduct derived from reaction with 9-hydroxy-BaP-4,5-oxide. In the presence of either of the reductase cofactors tested, NADPH or NADH, cytochrome b (5) stimulated CYP1A1-mediated formation of both BaP-DNA adducts. The results demonstrate that NADH can act as a sole electron donor for both the first and the second reduction of CYP1A1 during its reaction cycle catalyzing oxidation of BaP, and suggest that the NADH:cytochrome b (5) reductase as the NADH-dependent reductase might substitute POR in this enzymatic system.
Czech name
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Czech description
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Classification
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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Result continuities
Project
<a href="/en/project/GA15-02328S" target="_blank" >GA15-02328S: Organisms and mechanisms determining the fate of endocrine disruptors in the environment</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Monatshefte für Chemie
ISSN
0026-9247
e-ISSN
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Volume of the periodical
147
Issue of the periodical within the volume
5
Country of publishing house
AT - AUSTRIA
Number of pages
9
Pages from-to
847-855
UT code for WoS article
000374172200002
EID of the result in the Scopus database
2-s2.0-84960080220