Date of Award

1994

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

First Advisor

Co-Charles R. Short

Second Advisor

David H. Swenson

Abstract

This study characterized the oxidative biotransformation capacity of the hepatic cytochrome P-450 system of selected avian species representing the Galliformes (chicken, turkey and Japanese quail) and Anseriformes (goose, Pekin duck, Khaki Campbell duck, and Muscovy duck) orders. Two objectives were addressed; first, important biotransformation pathways were evaluated in economically major and minor food-producing avian species to provide a framework on which to base drug approval decisions in these species. Second, the potential use of the selected species as sentinel organisms utilizing cytochrome P-450 induction as a biomarker of environmental chemical exposure was evaluated. The male rat was utilized for the mammalian model and as a point of reference. Two groups of animals for each species were evaluated, a control group, which received no treatment, and a treatment group which was administered $\beta$-naphthoflavone ($\beta$NF). Investigations included the quantitation of microsomal protein, cytochrome P-450, NADH- and NADPH-cytochrome c reductase activity, ethoxyresorufin O-deethylase activity and benzo (a) pyrene hydroxylase activity with the development of profiles for four major metabolites. This study found that constitutive microsomal protein levels, cytochrome P-450 content, NADPH-cytochrome c reductase activities and ethoxyresorufin O-deethylase activities were similar among the species studied while NADH-cytochrome c reductase activities differed. In response to $\beta$NF, microsomal protein levels, cytochrome P-450 content, and ethoxyresorufin O-deethylase activities were increased but no change was observed in NADPH- or NADH-cytochrome c reductase activities. Interspecies differences were observed in the response of the hepatic microsomal system to $\beta$NF treatment. Interspecies differences were also observed in the capacity of the avian hepatic microsomal system to hydroxylate benzo (a) pyrene and in the effect of $\beta$NF treatment upon metabolite production. 3-Hydroxybenzo (a) pyrene was the primary metabolite produced by all the species studied; interspecies and interorder differences in product distributions were observed for the 9-hydroxybenzo (a) pyrene, benzo (a) pyrene 7,8-dihydrodiol and benzo (a) pyrene 9,10-dihydrodiol metabolites.

Pages

302

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