Role of P450 1A1 and P450 1A2 in Bioactivation versus Detoxication of the Renal Carcinogen Aristolochic Acid I: Studies in Cyp1a1(-/-), Cyp1a2(-/-), and Cyp1a1/1a2(-/-) Mice

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F11%3A10100499" target="_blank" >RIV/00216208:11310/11:10100499 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1021/tx200259y" target="_blank" >http://dx.doi.org/10.1021/tx200259y</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/tx200259y" target="_blank" >10.1021/tx200259y</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Role of P450 1A1 and P450 1A2 in Bioactivation versus Detoxication of the Renal Carcinogen Aristolochic Acid I: Studies in Cyp1a1(-/-), Cyp1a2(-/-), and Cyp1a1/1a2(-/-) Mice

Popis výsledku v původním jazyce

Exposure to aristolochic acid I (AAI) is associated with aristolochic acid nephropathy, Balkan endemic nephropathy, and urothelial cancer. Individual differences in xenobiotic-metabolizing enzyme activities are likely to be a reason for interindividual susceptibility to AA-induced disease. We evaluated the reductive activation and oxidative detoxication of AAI by cytochrome P450 (P450) 1A1 and 1A2 using the Cyp1a1(-/-) and Cyp1a2(-/-) single-knockout and Cyp1a1/1a2(-/-) double-knockout mouse lines. Incubations with hepatic microsomes were also carried out in vitro. P450 1A1 and 1A2 were found to (i) activate AAI to form DNA adducts and (ii) detoxicate it to 8-hydroxyaristolochic acid I (AAIa). AAI-DNA adduct formation was significantly higher in all tissues of Cyp1a1/1a2(-/-) than Cyp1a(+/+) wild-type (WT) mice. AAI-DNA adduct levels were elevated only in selected tissues from Cyp1a1 (-/-) versus Cyp1a2(-/-) mice, compared with those in WT mice. In hepatic microsomes, those from WT as

Název v anglickém jazyce

Role of P450 1A1 and P450 1A2 in Bioactivation versus Detoxication of the Renal Carcinogen Aristolochic Acid I: Studies in Cyp1a1(-/-), Cyp1a2(-/-), and Cyp1a1/1a2(-/-) Mice

Popis výsledku anglicky

Exposure to aristolochic acid I (AAI) is associated with aristolochic acid nephropathy, Balkan endemic nephropathy, and urothelial cancer. Individual differences in xenobiotic-metabolizing enzyme activities are likely to be a reason for interindividual susceptibility to AA-induced disease. We evaluated the reductive activation and oxidative detoxication of AAI by cytochrome P450 (P450) 1A1 and 1A2 using the Cyp1a1(-/-) and Cyp1a2(-/-) single-knockout and Cyp1a1/1a2(-/-) double-knockout mouse lines. Incubations with hepatic microsomes were also carried out in vitro. P450 1A1 and 1A2 were found to (i) activate AAI to form DNA adducts and (ii) detoxicate it to 8-hydroxyaristolochic acid I (AAIa). AAI-DNA adduct formation was significantly higher in all tissues of Cyp1a1/1a2(-/-) than Cyp1a(+/+) wild-type (WT) mice. AAI-DNA adduct levels were elevated only in selected tissues from Cyp1a1 (-/-) versus Cyp1a2(-/-) mice, compared with those in WT mice. In hepatic microsomes, those from WT as

Druh

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

CEP obor

CE - Biochemie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>Z - Vyzkumny zamer (s odkazem do CEZ)<br>S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2011

Kód důvěrnosti údajů

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

Název periodika

Chemical Research in Toxicology

ISSN

0893-228X

e-ISSN

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Svazek periodika

24

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

1710-1719

Kód UT WoS článku

000295817800013

EID výsledku v databázi Scopus

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