Date

June 1980

Document Type

Thesis

Degree Name

M.S.

Department

Dept. of Chemistry

Institution

Oregon Graduate Center

Abstract

Single doses of tetrachlorobiphenyls, shown to be free of any chlorinated dibenzodioxins or dibenzofurans to a level of 1 ppm, were given to rhesus monkeys (Macaca mulatta) and the hepatic microsomal enzyme response measured periodically for 32 days. Liver biopsies, obtained by a closed needle technique, provided the tissue samples. Aryl hydrocarbon hydroxylase (measured as benzo[a]pyrene hydroxylase), aminopyrine - N - demethylase and cytochrome P-450 were measured on each sample. Animals treated with 25 mg/kg body weight of 2,5,2' ,5'- tetrachlorobiphenyl showed a marked increase in the demethylase activity, which peaked at 1 to 2 days after treatment, and had no effect on the x hydroxylase activity or the position of the absorption maximum of the CO difference spectrum of cytochrome P-450. This is phenobarbital like inductive behavior. The animals treated with 1 mg/kg body weight of 3, 4, 3’, 4’-tetrachlorobiphenyl showed a 3-methylcholanthrene type inductive profile. The hydroxylase activity was significantly increased and peaked at 2 days after treatment. The demethylase activity was not changed. The position of the cytochrome P-450 difference spectrum absorption maximum was shifted to 448 nm. The control animals received just the acetone / corn oil vehicle and showed no changes in any of the biochemical activities measured in the course of this experiment. This data supports the structure activity relationships, established in rats, for chlorobiphenyls as inducers of hepatic microsomal enzyme activity in rhesus monkeys.

Identifier

doi:10.6083/M4RB72JR

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