Molecular genetics of the human cytochrome P-450 system.

barbital-type inducers in teleosts. T h e lack of PB-type induction in some groups (fish, reptilia, amphibia) must be due to either a lack of structural genejs) coding for PB-inducible forms, o r t o the lack of a regulatory mechanism like that acting to control expression of the related genes in mammals. T h e mechanism of PB induction has yet to be described. However, we recently obtained evidence indicating the identity of a fish cytochrome 1’-450 related to a major PBinducible form in mammals. We have detected single proteins in untreated fish liver microsomes that strongly cross-react with antibodies to mammalian PB-inducible P450 IlBl (rat P450b or PB4) (J. Stegeman, B. Woodin & D. Waxman, unpublished work). Antibodies to scup P450B [ 131 strongly recognize an identical band in these same species. T h e antiscup P450B also detected the same bands in PB-induced rats as seen by anti-P450 PB-4 (Table 3). Antibodies to the scup and rat proteins also recognized the antigens, scup P450B and rat P450 PB-4 (IIBl) , purified from these species. Defining relationships between these anti-P450 IIB 1 cross-reacting proteins in fish and the mammalian PB-inducible proteins, should help to focus our efforts to understand the lack of PB-response in fish, and could aid in identifying thc mechanism of PB induction. Further defining the spectrum of cytochromes 1’-450 in teleosts will enhance their utility as model systems in toxicology or carcinogenesis, as well as providing a basis for predicting susceptibility to environmental chemical effects in aquatic systems.