Abstract
KAMATAKI, T., KITADA, M., KOMORI, M., YOKOI, T. and KITAMURA, R. Human Fetal Liver Cytochrome P-450: Capacity to Form Genotoxic Metabolites. Tohoku J. Exp. Med., 1992, 168 (2), 89-95 - Unlike most experimental animals, human fetal liver possesses forms of cytochrome P-450. Thus, the purpose of this study was to clarify the toxicological significance of these forms of cytochrome P-450 to understand possibile roles of these cytochromes in producing genotoxic metabolites from promutagens. In fact, human fetal livers showed considerable capacity to activate aflatoxin B1 and IQ (2-amino-3-methylimidazo [4, 5-f] quinoline). Three of four forms of cytochrome P-450, P-454HFLa-d, which we could purify from human fetal livers were capable of activating promutagens to mutagens. One of these three forms, namely P-450HFLa, catalyzed the metabolic activation of aflatoxin B1 and IQ. An expression plasmid containing HFL33 cDNA encoding P-450HFLa was constructed and the protein expressed in insect (Sf9) cells and in human cancer cells, MCF-7. Aflatoxin B1 was efficiently activated to a mutagen upon addition of the lysate of Sf9 cells to the incubation mixture for the assay. Transformants of MCF-7 cells expressing P-450IIIA7 (HFLa) showed higher sensitivity to aflatoxin B1 than the parental MCF-7 cells as detected by cytotoxicity. - human fetal liver cytochrome P-450; genotoxic metabolites; aflatoxin B1; 2-amino-3-methylimidazo [4, 5-f] quinoline (IQ); transformation of MCF-7 cells
