Cytochrome P450-dependent monooxygenase activities and their inducibility by classic P450 inducers in the liver, kidney, and nasal mucosa of male adult ring-necked pheasants

In this study, several P450-dependent monoxygenase activities in the liver, kidney, and nasal mucosa of ring-necked pheasants were examined. In additi on, the presence and inducibility of P450 isoenzymes in the hepatic and ren al tissues of pheasants were examined by using typical substrates and induc ers of P450s along with polyclonal antibodies raised against mammalian isof orms. Anti-rat P450 1A1 recognized in microsomes of both pheasant liver and kidney a protein that was markedly induced by P-naphthoflavone and accompa nied by an increase of various monooxygenases, in particular, methoxyresoru fin-O-demethylase (MROD) activity. Anti-rat P450 2E1 revealed in microsomes of the pheasant liver but not in kidney an immunoreactive protein that was slightly induced by acetone but not accompanied by an increase of para-nit rophenol hydroxylase activity. On the other hand, acetone treatment caused an induction of other hepatic monoxygenases including MROD, erythromycin N- demethylase, and 6 beta-testosterone hydroxylase. These two latter activiti es, known to be markers for 3A isoenzymes in rodents, were also enhanced in pheasant liver by phenobarbital but not by dexamethasone. The treatment wi th these two inducers also lacked to point out hepatic and renal proteins i mmunorelated to P450 3A or 2B subfamily, suggesting that these isoforms may be not expressed in pheasant. On the other hand, anti-rat P450 2C11 recogn ized two immunorelated proteins in the liver of both control and treated ph easants. The treatment with clofibrate, a mammalian inducer of 4A subfamily , induced both in liver and kidney of pheasant: i) a protein that cross-rea cted with anti rat P450 4A1 and ii) the (omega) and (omega-1) lauric acid h ydroxylase activities, known to be associated in mammals to this P450 subfa mily. In the nasal mucosa of pheasant, a protein immunorelated to P450 2A a nd some monooxygenase activities (i.e., 7-ethoxycoumarin O-deethylase) link ed, in mammals, to this isoform have been found; by contrast a protein immu noreactive with anti P450 2G1 was not found. In conclusion, the immunochemi cal properties and monooxygenase activities of constitutive and inducible P 450s in pheasants were different not only from those of mammals but also fr om those of chickens. The findings of the present work also suggest that th e P450 induction profiles might provide a potential biomarker of pheasant e xposure to chemicals or environmental pollutants in the wild-field or in th e stock-farm. (C) 2000 Academic Press.