Relationship between Chemical Structure and Activity. III. Dose-Response or Time-Course of Induction in Microsomal Enzymes Following Treatment with 1, 2, 4-Trichlorobenzene

The contents of hepatic constituents and cytochromes as well as the activities of drug-metabolizing enzymes and δ-aminolevulinic acid (δ-ALA) synthetase were determined in rats treated with 1, 2, 4-trichlorobenzene (1, 2, 4-TRCB). 1) Liver weight and microsomal protein content were increased in higher doses than 750 mg/kg 24 hr after the administration, but in contrast glycogen content was markedly decreased in higher doses than 500 mg/kg. In a dose of 250 mg/kg and above, the activities of aminopyrine demethylase and aniline hydroxylase, cytochrome P-450 contenn were increased, but on the contrary cytochrome b5 content showed the tendency to be decreased in high doses. δ-ALA synthetase activity was increased in higher doses than 250 mg/kg, and this increase attained approximately 300% in higher doses than 750 mg/kg. 2) In a single oral dose of 500 mg/kg, glycogen content was decreased markedly from 6 hr after the administration and this decrease was maintained for 48 hr. The increase of microsomal protein content was noted in 3 hr after dosing, but cytochrome P-450 content, activities of aminopyrine demethylase and aniline hydroxylase were increased 24 hr after the administration. These increases were maintained for 5 days, especially in aminopyrine demethylase for 15 days. δ-ALA synthetase activity was decreased markedly in the early stage, that is, 3 or 6 hr after the administration, but increased rapidly after 24 hr. 3) An apparent parallelism between the change in δ-ALA synthetase activity and that in cytochrome P-450 content was not noted.