Ellipticine oxidation and DNA adduct formation in human hepatocytes is catalyzed by human cytochromes P450 and enhanced by cytochrome b5

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F12%3A10126398" target="_blank" >RIV/00216208:11310/12:10126398 - isvavai.cz</a>
Alternative codes found
RIV/61989592:15110/12:33139859
Result on the web
<a href="http://dx.doi.org/10.1016/j.tox.2012.08.004" target="_blank" >http://dx.doi.org/10.1016/j.tox.2012.08.004</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.tox.2012.08.004" target="_blank" >10.1016/j.tox.2012.08.004</a>

Result language
angličtina
Original language name
Ellipticine oxidation and DNA adduct formation in human hepatocytes is catalyzed by human cytochromes P450 and enhanced by cytochrome b5
Original language description
Ellipticine is an antineoplastic agent considered a pro-drug, the pharmacological and genotoxic effects of which are dependent on cytochrome P450 (CYP)- and/or peroxidase-mediated activation to covalent DNA adducts. We investigated whether ellipticine-DNA adducts are formed in human hepatic microsomes and human hepatocytes. We then identified which human CYPs oxidize ellipticine to metabolites forming DNA adducts and the effect of cytochrome b5 on this oxidation. 13-Hydroxyellipticine, the metabolite forming the major ellipticine-DNA adduct, was generated mainly by CYP3A4 and 1A1, followed by CYP2D6 > 2C19 > 1B1 > 1A2 > 2E1 and >2C9. Cytochrome b5 increased formation of this metabolite by human CYPs, predominantly by CYP1A1, 3A4, 1A2 and 2C19. Formation of 12-hydroxyellipticine is generated mainly by CYP2C19, followed by CYP2C9 > 3A4 > 2D6 > 2E1 and >2A6. Other CYPs were less active (CYP2C8 and 2B6) or did not oxidize ellipticine to this metabolite (CYP1A1, 1A2 and 1B1). CYP2D6 was the
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
<a href="/en/project/GAP301%2F10%2F0356" target="_blank" >GAP301/10/0356: Study of contribution of different DNA-damaging mechanisms to toxicity of cytostatics to human chemosensitive and chemoresistant neuroblastomas</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<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

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