Molecular toxicology on cytochrome P-450 in human fetal livers.
Among mammalian species, humans and monkeys are sole species which possess cytochrome P-450 in the liver in fetal life. Cytochrome P-450 catalyzes oxidations of a wide variety of compounds including steroids, drugs and toxicants. Thus, the purpose of this study was to examine the toxicological significance of human fetal cytochrome P-450. Firstly, we found that human fetal livers were capable of activating numbers of carcinogenic compounds. Secondly, the capacity of human fetal cytochrome P-450 to activate mutagens and carcinogens was confirmed using purified forms of cytochrome P-450. For this, we purified four forms of cytochrome P-450 from human fetal livers. Lastly, we could isolate a cDNA clone coding for P-450HFLa which is one of the major forms of cytochrome P-450 in human fetal livers. Utilizing synthesized cD-NAs as probes, we found that this form of cytochrome was expressed specifically in fetuses.
Kamataki
T
T
Division of Analytical Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Kitada
M
M
Komori
M
M
D001711:Biotransformation; D002273:Carcinogens / Q000493:pharmacokinetics; D003001:Cloning, Molecular; D003577:Cytochrome P-450 Enzyme System / Q000302:isolation & purification / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005260:Female; D005333:Fetus / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000196:embryology / Q000201:enzymology*; D009153:Mutagens / Q000493:pharmacokinetics; D011247:Pregnancy; D014407:Tumor Cells, Cultured / Q000378:metabolism
D002273:Carcinogens; D004273:DNA, Neoplasm; D009153:Mutagens; D003577:Cytochrome P-450 Enzyme System