Bioactivation versus Detoxication of the Urothelial Carcinogen Aristolochic Acid I by Human Cytochrome P450 1A1 and 1A2

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F12%3A10125577" target="_blank" >RIV/00216208:11310/12:10125577 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1093/toxsci/kfr306" target="_blank" >http://dx.doi.org/10.1093/toxsci/kfr306</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/toxsci/kfr306" target="_blank" >10.1093/toxsci/kfr306</a>

Result language

angličtina

Original language name

Bioactivation versus Detoxication of the Urothelial Carcinogen Aristolochic Acid I by Human Cytochrome P450 1A1 and 1A2

Original language description

Exposure to aristolochic acid (AA) is associated with human nephropathy and urothelial cancer. Individual susceptibility to AA-induced disease likely reflects individual differences in enzymes that metabolize AA. Herein, we evaluated AAI metabolism by human cytochrome P450 (CYP) 1A1 and 1A2 in two CYP1A-humanized mouse lines that carry functional human CYP1A1 and CYP1A2 genes in the absence of the mouse Cyp1a1/1a2 orthologs. Human and mouse hepatic microsomes and human CYPs were also studied. Human CYP1A1 and 1A2 were found to be principally responsible for reductive activation of AAI to form AAI-DNA adducts and for oxidative detoxication to 8-hydroxyaristolochic acid (AAIa), both in the intact mouse and in microsomes. Overall, AAI-DNA adduct levels were higher in CYP1A-humanized mice relative to wild-type mice, indicating that expression of human CYP1A1 and 1A2 in mice leads to higher AAI bioactivation than in mice containing the mouse CYP1A1 and 1A2 orthologs. Furthermore, an exclusi

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

CE - Biochemistry

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

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<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2012

Confidentiality

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

Name of the periodical

Toxicological Sciences

ISSN

1096-6080

e-ISSN

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Volume of the periodical

125

Issue of the periodical within the volume

2

Country of publishing house

GB - UNITED KINGDOM

Number of pages

14

Pages from-to

345-358

UT code for WoS article

000299346000004

EID of the result in the Scopus database

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