Knockout and humanized mice as suitable tools to identify enzymes metabolizing the human carcinogen aristolochic acid
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem, přehledy
Grantová podpora
14329
Cancer Research UK - United Kingdom
- MeSH
- adukty DNA metabolismus MeSH
- cytochrom P-450 CYP1A1 genetika metabolismus MeSH
- cytochrom P-450 CYP1A2 genetika metabolismus MeSH
- enzymy genetika metabolismus MeSH
- inhibitory enzymů farmakologie MeSH
- karcinogeny metabolismus farmakokinetika MeSH
- kyseliny aristolochové metabolismus farmakokinetika toxicita MeSH
- lidé MeSH
- metabolická inaktivace * MeSH
- myši knockoutované * MeSH
- myši MeSH
- NAD(P)H dehydrogenasa (chinon) antagonisté a inhibitory MeSH
- NADPH-cytochrom c-reduktasa genetika metabolismus MeSH
- nemoci ledvin chemicky indukované MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- adukty DNA MeSH
- aristolochic acid I MeSH Prohlížeč
- CYP1A1 protein, human MeSH Prohlížeč
- CYP1A2 protein, human MeSH Prohlížeč
- cytochrom P-450 CYP1A1 MeSH
- cytochrom P-450 CYP1A2 MeSH
- enzymy MeSH
- inhibitory enzymů MeSH
- karcinogeny MeSH
- kyseliny aristolochové MeSH
- NAD(P)H dehydrogenasa (chinon) MeSH
- NADPH-cytochrom c-reduktasa MeSH
- NQO1 protein, human MeSH Prohlížeč
UNLABELLED: 1. Aristolochic acid I (AAI) is the predominant component in plant extract of Aristolochia genus that is involved in development of aristolochic acid nephropathy, Balkan endemic nephropathy and urothelial cancer. The diseases do not develop in all individuals exposed to AAI and patients exhibit different clinical outcomes. Differences in the activities of enzymes catalyzing the metabolism of AAI might be one of the reasons for this individual susceptibility. 2. Understanding which human enzymes are involved in reductive activation of AAI generating AAI-DNA adducts, and/or its detoxication to the O-demethylated metabolite, aristolochic acid Ia (AAIa), is necessary in the assessment of the susceptibility to this compound. 3. This review summarizes the results of the latest studies utilizing genetically engineered mouse models to identify which human and rodent enzymes catalyze the reductive activation of AAI to AAI-DNA adducts and its oxidative detoxication to AAIa in vivo. 4. The use of hepatic cytochrome P450 (Cyp) reductase null (HRN) mice, in which NADPH:Cyp oxidoreductase (Por) is deleted in hepatocytes, Cyp1a1((-/-)), Cyp1a2((-/-)) single-knockout, Cyp1a1/1a2((-/-)) double-knockout and CYP1A-humanized mice revealed that mouse and human CYP1A1 and 1A2, besides mouse NAD(P)H: quinone oxidoreductase, were involved in the activation of AAI but CYP1A1 and 1A2 also oxidatively detoxified AAI.
Citace poskytuje Crossref.org
The impact of p53 on aristolochic acid I-induced nephrotoxicity and DNA damage in vivo and in vitro
Balkan endemic nephropathy: an update on its aetiology
