The impact of individual cytochrome P450 enzymes on oxidative metabolism of benzo[a]pyrene in human livers
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F16%3A10323063" target="_blank" >RIV/00216208:11310/16:10323063 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1002/em.22001" target="_blank" >http://dx.doi.org/10.1002/em.22001</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/em.22001" target="_blank" >10.1002/em.22001</a>
Alternative languages
Result language
angličtina
Original language name
The impact of individual cytochrome P450 enzymes on oxidative metabolism of benzo[a]pyrene in human livers
Original language description
Benzo[a]pyrene (BaP) is a human carcinogen that covalently binds to DNA after metabolic activation by cytochrome P450 (CYP) enzymes. In this study human recombinant CYPs (CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C19, 2E1, 3A4, and 3A5) were expressed in Supersomes together with their reductases, NADPH:CYP oxidoreductase, epoxide hydrolase and cytochrome b(5), to investigate BaP metabolism. Human CYPs produced up to eight BaP metabolites. Among these, BaP-7,8-dihydrodiol and BaP-9-ol, which are intermediates in BaP-derived DNA adduct formation, were mainly formed by CYP1A1 and 1B1, and to a lesser extent by CYP2C19 and 3A4. BaP-3-ol, a metabolite that is a detoxified' product of BaP, was formed by most human CYPs tested, although CYP1A1 and 1B1 produced it the most efficiently. Based on the amounts of the individual BaP metabolites formed by these CYPs and their expression levels in human liver, we determined their contributions to BaP metabolite formation in this organ. Our results indicate that hepatic CYP1A1 and CYP2C19 are most important in the activation of BaP to BaP-7,8-dihydrodiol, whereas CYP2C19, 3A4, and 1A1 are the major enzymes contributing to the formation of BaP-9-ol. BaP-3-ol is predominantly formed by hepatic CYP3A4, while CYP1A1 and 2C19 are less active. Environ. Mol. Mutagen. 57:229-235, 2016. (c) 2016 The Authors. Environmental and Molecular Mutagenesis Published by Wiley Periodicals, Inc.
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
Environmental and Molecular Mutagenesis
ISSN
0893-6692
e-ISSN
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Volume of the periodical
57
Issue of the periodical within the volume
3
Country of publishing house
US - UNITED STATES
Number of pages
7
Pages from-to
229-235
UT code for WoS article
000372722100006
EID of the result in the Scopus database
2-s2.0-84960443957