Cytochrome P450 enzymes in the kidney of the bobwhite quail (Colinus virginianus): induction and inhibition by ergosterol biosynthesis inhibiting fungicides

Metabolism of testosterone and the alkoxyresorufins was examined in kidney microsomes from male Bobwhite quail (Colinus virginiamus) and was compared with that in kidney microsomes prepared from the male rat. In addition, cro ss-reactivity studies were conducted with a number of antibodies prepared a gainst cytochrome P450 (CYP) enzymes purified from rat and trout liver. The effects of treatment with the fungicides: propiconazole, vinclozolin, clot rimazole and ketoconazole were examined. While kidney microsomes from both quail and rat catalyzed testosterone metabolism at multiple positions, the pattern of hydroxylated metabolites differed. Treatment with vinclozolin re sulted in significant induction of testosterone 2 beta- and 15 beta-hydroxy lase activity in quail kidney accompanied by increases in expression of P45 0 enzymes cross-reactive with antibodies raised against a CYP 3A-like prote in in teleost fish. In contrast, ketoconazole treatment resulted in inhibit ion of testosterone hydroxylation at positions 15 beta- and 6 alpha-. Propi conazole and vinclozolin significantly induced a CYP 1A1 cross-reactive P45 0 enzyme in quail kidney 2-3-fold unaccompanied by significant increases in alkoxyresorufin O-dealkylase activity. These activities were significantly inhibited by ketoconazole treatment. Quail kidney microsomes also expresse d high levels of a CYP 4A1 cross-reactive apoprotein which was inducible 3- 4-fold by ketoconazole. Thus, quail kidney possesses cytochrome P450 enzyme s related to forms found in mammalian gene families 1, 3 and 4. Fungicide t reatment results in mixed patterns of induction and inhibition of kidney P4 50 enzymes different from those previously reported in quail liver. (C) 199 8 Elsevier Science Inc. All rights reserved.