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  • Title: Ontogeny of the chicken cytochrome P-450 enzyme system. Expression and development of responsiveness to phenobarbital induction.
    Author: Lorr NA, Bloom SE.
    Journal: Biochem Pharmacol; 1987 Sep 15; 36(18):3059-67. PubMed ID: 3632724.
    Abstract:
    The sensitivity of the developing embryo to toxins and drugs is highly dependent on the state of development of the cytochrome P-450 system. Previous work in this laboratory has demonstrated the genotoxicity of aflatoxin B1 (AFB1) to the chicken embryo at 3 days of incubation (DI) and induction of AFB1 genotoxicity by phenobarbital at 7 DI. In this study, the basal and 24-hr phenobarbital (PB) induced levels of aminopyrine-N-demethylase (AMPD) and cytochrome P-450 were assayed in hepatic microsomes from 7 DI to 36 days posthatching (PH) and in microsomes from whole embryos at 5 DI. A dose-response for induction by PB was observed in embryonic hepatic microsomes as early as 7 DI, whereas a low level of cytochrome P-450 was detected in control 7 DI microsomes using the reduced CO vs oxidized CO difference spectrum. Basal levels of AMPD and cytochrome P-450 in hepatic microsomes increased steadily throughout development as did the responsiveness of the embryonic liver to induction with PB. Hepatic microsomes from control and PB-induced chickens had the highest AMPD activities posthatching particularly from 1 to 3 days PH. Maximal induced levels, which were 2- to 3-fold over control throughout development, ranged from 1.22 at 7 DI to 12.72 nmol HCHO/mg protein/min at 2 days PH. The potency of PB as an inducer increased about 1000-fold between 7 DI and hatching. PB induction did not increase the specific activity of AMPD at any period of development. The specific activity of AMPD posthatching increased about 3-fold above embryonic levels, indicating the development of a cytochrome P-450 complex more active toward aminopyrine in the neonatal period.
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