Metabolism of trichloroethylene in liver microsomes. 3. Induction of the enzymic activity and its effect on excretion of metabolites.

Abstract

The conversion of trichloroethylene to chloral hydrate by rat liver microsomal preparations has been shown to be increased when rats were pretreated with phenobarbital or exposed to atmospheres containing trichloroethylene. This increase was shown to be due to changes in the microsomal fraction and not in the soluble supporting enzyme systems. Unlike those of nonpretreated rats, the liver-soluble systems of phenobarbital-pretreated rats were unable to support the reaction optimally unless substrates of NADP-requiring dehydrogenases were added. Kinetic studies showed no difference in apparent Km between control and induced microsomal preparations. Induction of trichloroethylene-oxidizing activity by phenobarbital could not be shown in organs other than liven. Excretion of trichloroacetate and of unconjugated trichloroethanol after exposure to trichloroethylene was more rapid in rats pretreated with phenobarbital than in controls, although eventual cumulative excretions tended to be the same in both groups of animals. Excretion of urochloralic acid (trichloroethanol glucuronide) showed the greatest increase in rate upon phenobarbital pretreatment, and the cumulative output of this metabolite by pretreated rats was about twice that by controls at a time when its excretion had virtually ceased.