Role of Cytochromes P450 1A1/2 in Detoxication and Activation of Carcinogenic Aristolochic Acid I: Studies with the Hepatic NADPH:Cytochrome P450 Reductase Null (HRN) Mouse Model

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F11%3A10100497" target="_blank" >RIV/00216208:11310/11:10100497 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11130/11:7022
Result on the web
<a href="http://dx.doi.org/10.1093/toxsci/kfr050" target="_blank" >http://dx.doi.org/10.1093/toxsci/kfr050</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/toxsci/kfr050" target="_blank" >10.1093/toxsci/kfr050</a>

Result language
angličtina
Original language name
Role of Cytochromes P450 1A1/2 in Detoxication and Activation of Carcinogenic Aristolochic Acid I: Studies with the Hepatic NADPH:Cytochrome P450 Reductase Null (HRN) Mouse Model
Original language description
Aristolochic acid (AA) causes aristolochic acid nephropathy, Balkan endemic nephropathy, and their urothelial malignancies. To identify enzymes involved in the metabolism of aristolochic acid I (AAI), the major toxic component of AA we used HRN (hepaticcytochrome P450 [Cyp] reductase null) mice, in which NADPH:Cyp oxidoreductase (Por) is deleted in hepatocytes. AAI was demethylated by hepatic Cyps in vitro to 8-hydroxy-aristolochic acid I (AAIa), indicating that less AAI is distributed to extrahepaticorgans in wild-type (WT) mice. Indeed, AAI-DNA-adduct levels were significantly higher in organs of HRN mice, having low hepatic AAI demethylation capacity, than in WT mice. Absence of AAI demethylation in HRN mouse liver was confirmed in vitro; hepaticmicrosomes from WT, but not from HRN mice, oxidized AAI to AAIa. To define the role of hepatic Cyps in AAI demethylation, modulation of AAIa formation by CYP inducers was investigated. We conclude that AAI demethylation is attributable ma
Czech name
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Czech description
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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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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

Publication year
2011
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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