title: Four forms of cytochrome P-450 in human fetal liver: purification and their capacity to activate promutagens.
abstract: Four forms of cytochrome P-450 were separated and purified to electrophoretic homogeneity from human fetal livers. These forms of cytochrome P-450, termed P-450HFLa, P-450HFLb, P-450HFLc and P-450HFLd, were distinguishable from each other in their molecular weights, spectral properties, immunochemical properties and mutagen-producing activities from promutagens. The molecular weights of P-450HFLa, b, c and d were estimated to be 51,500, 49,000, 51,500 and 50,000, respectively. Antibodies to P-450HFLa recognized P-450HFLc but not P-450HFLb or d, and antibodies to rat P-448-H (P-450IA2) cross-reacted with P-450HFLb but not with other forms of cytochrome P-450. The N-terminal amino acid sequence of P-450HFLc was highly homologous, but not identical, to that of P-450HFLa. Each form of cytochrome P-450 catalyzed mutagenic activation of aflatoxin B1 (AFB1), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-6-methyldipyrido-[1,2-a:3',2'-d]imidazole (Glu-P-1) at different rates. P-450 HFLa showed activities to produce mutagen(s) from AFB1, IQ and to a lesser extent from Glu-P-1. P-450 HFLb activated IQ at a faster rate than did the other forms. P-450 HFLc produced a mutagen from AFB1 and Glu-P-1 but not from IQ. P-450 HFLd did not activate these promutagens at significant rates.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo.
authors.forename: M
authors.initials: M
authors.lastname: Kitada
authors.forename: M
authors.initials: M
authors.lastname: Taneda
authors.forename: K
authors.initials: K
authors.lastname: Itahashi
authors.forename: T
authors.initials: T
authors.lastname: Kamataki
mesh_terms: D002848:Chromatography, DEAE-Cellulose; D003577:Cytochrome P-450 Enzyme System / Q000302:isolation & purification* / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005333:Fetus / Q000201:enzymology*; D006801:Humans; D008099:Liver / Q000201:enzymology*; D009153:Mutagens / Q000378:metabolism; D013045:Species Specificity
chemical_list: D009153:Mutagens; D003577:Cytochrome P-450 Enzyme System