Four Forms of Cytochrome P‐450 in Human Fetal Liver: Purification and Their Capacity to Activate Promutagens

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 promntagens. 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 Bl (AFB1), 2‐amino‐3‐methylimidazo[4,5‐f]quinoline (IQ) and 2‐amino‐6‐methyldipyrido‐[l,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.