CHICK-EMBRYO LIVER MICROSOMAL STEROID HYDROXYLATIONS - INDUCTION BY DEXAMETHASONE, PHENOBARBITAL, AND GLUTETHIMIDE AND INACTIVATION FOLLOWING THE IN OVO ADMINISTRATION OF PORPHYRINOGENIC COMPOUNDS

Metabolites of [4-C-14]androstenedione (AD) and [4-C-14]progesterone ( PG) were separated and quantitated following incubation with hepatic m icrosomes from chick embryos. PG 2 alpha-hydroxylase and AD 7 alpha-hy droxylase, which are diagnostic markers in rat liver for cytochrome P4 50 (P450) 2C11 and 2A1/2, respectively, were not identified in chick e mbryo liver. PG 6 beta-hydroxylase and AD 6 beta-hydroxylase, diagnost ic markers for P450 3A1/2 activity in rat liver, were identified in ch ick embryo liver, and we were able to show that radiolabeled 6 beta-hy droxyprogesterone and 6 beta-hydroxyandrostenedione, the metabolites o f PG and AD 6 beta-hydroxylase, respectively, were homogeneous and ide ntical with authentic standards. Dexamethasone, phenobarbital, and glu tethimide were found to be significant inducers of PG and AD 6 beta-hy droxylases in chick embryo liver. The in ovo administration of the por phyrinogenic compounds ycarbonyl-1,4-dihydro-2,6-dimethyl-4-ethylpyrid ine (4-ethyl DDC) and -(2,4,6-trimethylphenyl)-thioethyl]4-methylsydno ne (TTMS) caused inactivation of chick embryo hepatic PG and AD 6 beta -hydroxylases, Therefore, we suggest that PG and AD 6 beta-hydroxylase s may serve as diagnostic markers for a P450 3A-like isozyme in the ch ick embryo, and that this isozyme is one of the targets for inactivati on by 4-ethyl DDC and TTMS.