Age Related Changes in the Induction of Hepatic Mixed-Function Monooxygenase System in Miniatures Pigs: Effects of Pentachlorianisole, Pentachlorophenol and Phenobarbital

摘要: Agins, Alan P., Ph.D., University of Rh ode Jsland, 198 2 . Age Related Changes in the Induct ion He patic Mixed-Function Monooxygenase Syst e m Mini ature Pigs: Effects Pentachloroanisole, Pentachlorophenol and Phenobarbital. Major Professor: Dr. George C. Fuller. Pentachloroanisole (PCA), an environmental degradation product biocide pentachlorophenol (PCP), has been detected food chain. The metabolic fate PCA was xamined miniature pig hepatic microsomes, vitro. compound shown to be a substrate for cytochrome P450-dependent demethylation reaction, which results regeneration par nt compound, PCP. A disproportionately large increase demethylase activity (PCADM) following pretreatment with phenobarbital suggests that is preferentially metabolized by specific-inducible form(s) P450. comparison effects purified PCP on MFO system pigs conducted at various stages postnatal development. Phenobarbital utilized as positive control induction. PCA, (10 mg/kg/day X 4 days, P.O.) were administered piglets 1, 4, 8 weeks age levels cytochromes P450 b 5 , activities NADPH-Cytochrome c reductase, aniline hydroxylase (ANOH), p-nitroanisole (NADM), determined. In one week old piglets, pr od uc ed significant increases Rll panimete rs measured, greatest effect (300% contro l ) its own vitro metabo li sm pleiotropic response> evok0d !'Ci\ simi r phenobarbita but o( esser magnLt ud produ ce d sma ll only ;rnd nitroanisole deme thyl;:ise Th qualitative differences th induction patterns produce nd two compou s xert diff rent effec t o n By eight age, h magnitude diminishe d. Furthermore, although specific ANOH NADM, PCADM ph nobarbital treated simil ar 1 examination catalytic acti vit y profiles suggested dependent decrease induct speci f ie forms On further investigation, Eadie-Hof~tee plots from kinetic experiments ex ibited biphasic patter suggestive multiple P45Q catalyzing same eactio integrating ffects treatment species each substrate, minimum four are xi st miniatur microsomes. Of forms, inducible nobarb ita ese appears displ ay -de pende ncy se data indica xogenous chemicals varies qualitatively well quantitati vely