Occurrence and inducibility of cytochrome P 450IIIA in maternal and fetal rats during prenatal development

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Abstract
The purpose of this study was to quantify cytochrome P450IIIA1 in fetal and maternal livers of uninduced the pregnenolone-16.alpha.-carbonitrile (PCN) induced rats during the course of prenatal development. The activities and levels of P450IIIA in hepatic microsomes from maternal rats and fetuses at 15-21 days of gestation were measured by triacetylolenadomycin (TAO) inhibited debenzylation of (benzyloxy)phenoxazone and by immunoassay with defined antiserum specific for P45OIIIA. P450IIIA was not detectable (< 10 pmol/mg for maternal microsomes and < 2 pmol/mg for fetal microsomes) by immunoassay in uninduced maternal or fetal livers. In hepatic microsomes from PCN-induced dams, values ranged from 59.3 to 116 .mu.g P450IIIA1/mg of protein during the same gestational period. Changes in debenzylase activity of 15.9-46.5 pmol of resorufin (mg of protein)-1 min-1 were consistent with these findings as were the changes in TAO-inhibitable debenzylase activity. In the transplacentally induced fetal liver, debenzylase activity increased steadily from 0.19 pmol of resorufin mg-1 min-1 at day 15 to 9.34 pmol of resorufin mg-1 at day 21 and was paralleled by the TAO-inhibitable activity that ranged from 0.09 pmol of resorufin mg-1 min-1 at day 15 to 3.33 pmol of resorufin mg-1 min-1 at day 21. The amount of immunoreactive P450IIIA1 also increased from 0.5 to 28.7 .mu.g/mg of microsomal protein. When the dose of PCN used to induce the maternal animals was increased from 50 mg/kg, once daily for 3 days, to 40 mg/kg, twice daily for 4 days, fetal debenzylase activity was decreased by approximately 10-20% over the gestational period as was the TAO-inhibited debenzylase activity. Analogously, immunoreactive P450IIIA1 was also slightly decreased. The data indicate that P450IIIA1 in fetal rat liver is PCN-inducible as early as day 15 of gestation and that inducibility progressively increases as a function of fetal age.

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