The impact of individual cytochrome P450 enzymes on oxidative metabolism of benzo[a]pyrene in human livers

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

The impact of individual cytochrome P450 enzymes on oxidative metabolism of benzo[a]pyrene in human livers

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

The impact of individual cytochrome P450 enzymes on oxidative metabolism of benzo[a]pyrene in human livers

Popis výsledku anglicky

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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CE - Biochemie

OECD FORD obor

—

Projekt

<a href="/cs/project/GA15-02328S" target="_blank" >GA15-02328S: Organismy a mechanismy určující osud endokrinních disruptorů v životním prostředí</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Environmental and Molecular Mutagenesis

ISSN

0893-6692

e-ISSN

—

Svazek periodika

57

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

7

Strana od-do

229-235

Kód UT WoS článku

000372722100006

EID výsledku v databázi Scopus

2-s2.0-84960443957