PMID: 7581497Jan 1, 1995Paper

Cytochrome P450 mediated reactions studied in genetically engineered V79 Chinese hamster cells

Pharmacogenetics
J DoehmerJ Jacob

Abstract

V79 Chinese hamster cells genetically engineered for stable expression of rat and human CYP have been shown to serve as analytical tools for studying metabolism related problems in toxicology and pharmacology. Here, the application of rat and human CYP1A1 and CYP1A2 is demonstrated for comparative studies on the oxidation of polycyclic aromatic hydrocarbons, such as phenanthrene, benz[a]anthracene, and benzo[a]pyrene. Live cells were cultivated for 2 days in the presence of these chemicals. Thereafter, the supernatant medium was checked for metabolites by gas chromatography and mass spectrometry. Marked cytochromes P450 and species dependent differences in the metabolite profiles were observed. Most important was the finding, that human cytochrome P450 1A1 almost exclusively oxidized benzo[a]pyrene in the 7,8,9,10-position, yielding the ultimate carcinogen 7,8-dihydroxy-9,10-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene whereas the rat cytochrome P450 1A1 oxidized benzo[]pyrene in the 4,5-position and 7,8,9,10-position. The importance of this finding is underlined by results from cytotoxicity studies. Benzo[a]pyrene was twice as cytotoxic in the human cytochrome P450 1A1 than in the rat cytochrome P450 1A1 expressing V79 cells. Spec...Continue Reading

Citations

Apr 26, 2012·Chemical Research in Toxicology·Slobodan Rendic, F Peter Guengerich
Oct 14, 2000·Archives of Biochemistry and Biophysics·N BlumeJ Fishman
Jul 26, 2011·Environmental and Molecular Mutagenesis·Shinsuke MarumotoMitsuo Miyazawa
Oct 27, 2004·Chemico-biological Interactions·Linda BerganderUlf Rannug
Apr 4, 2006·Chemico-biological Interactions·Wolfgang SchoberAlbrecht Seidel
Mar 1, 2005·Basic & Clinical Pharmacology & Toxicology·Ulrike BernauerUrsula Gundert-Remy
Dec 23, 2004·Alternatives to Laboratory Animals : ATLA·María José Gómez-LechónJosé V Castell
Sep 15, 2007·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Beate PeschThomas Brüning
Dec 22, 1999·Journal of Agricultural and Food Chemistry·K KanazawaG i Danno

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