Abstract

A detailed study was performed on the age and sex differences in the activity of the enzyme in the livers of rats which catalyzes the oxidation of thiophosphates. It was found that the enzyme activity of the livers of adult males was 2 to 3 times greater than that of adult females of the same age. No sex difference in enzyme activity was noted in animals less than 30 days of age but the activity of the livers of male rats exhibited an abrupt increase between 30 and 60 days of age which corresponds to the age of puberty in male rats. The low enzyme activity of the livers of adult females and young males was increased by prolonged administration of testosterone and the high activity of the livers of adult males was decreased by castration and by the prolonged administration of progesterone and diethylstilbestrol. The results of these experiments indicated that sex hormones influence the synthesis of the thiophosphate-oxidizing enzyme.

The activity of the thiophosphate-oxidizing enzyme of the regenerating livers of male rats was markedly decreasedat 4 days after partial hepatectomy but gradually returned to the normal level within 20 days. The low enzyme activity of the livers of adult females, weanling males and partially hepatectomized males is increased to the level of adult males at 24 hours after the administration of 25 mg/kg of 3-methylcholanthrene. 3,4-benzpyrene and 1,2,5,6-dibenzanthracene also increased the activity of the livers of adult female rats. The administration of ethionine inhibited the response to the hydrocarbons. The inhibition of cholinesterase caused by the intraperitoneal administration of 2 mg/kg of guthion was increased by approximately 50% at 48 hours after injection of methylcholanthrene. The intraperitoneal administration of 20 mg/kg of β-diethylaminoethyl diphenylpropylacetate (SKF 525A) 40 minutes before injection of 2 mg/kg of guthion markedly decreased the inhibition of cholinesterase and reduced susceptibility to the acute toxicity of guthion. These effects are explainable on the basis of the ability of SKF 525A to inhibit the enzymatic oxidation of thiophosphates.

Feeding a protein-free diet to adult male rats reduced the ability of the liver to convert guthion to an anticholinesterase agent by 75%. The increase in activity of the thiophosphate-oxidizing enzyme which occurs after the administration of carcinogenic hydrocarbons was inhibited when the animals were fed a protein-free diet.