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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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-

Název v anglickém jazyce

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

Popis výsledku anglicky

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-

Druh

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

CEP obor

CE - Biochemie

OECD FORD obor

—

Projekt

<a href="/cs/project/GAP301%2F10%2F0356" target="_blank" >GAP301/10/0356: Studie participace specifických mechanismů poškození DNA na cytoxicitě cytostatik vůči lidským chemosensitivním a chemorestentním neuroblastomům</a><br>

Návaznosti

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2014

Kód důvěrnosti údajů

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

Název periodika

Toxicology

ISSN

0300-483X

e-ISSN

—

Svazek periodika

318

Číslo periodika v rámci svazku

APR 6 2014

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

12

Strana od-do

1-12

Kód UT WoS článku

000335429300001

EID výsledku v databázi Scopus

—