Relationship between Chemical Structure and Activity. I. Effects of the Number of Chlorine Atoms in Chlorinated Benzenes on the Components of Drug-Metabolizing System and the Hepatic Constituents

To elucidate the relationship between chemical structure and their biological activities, the contents of cytochromes and hepatic constituents in addition to the activities of drug-metabolizing enzymes and δ-aminolevulinic acid (δ-ALA) synthetase were examined in rats treated with various chlorinated benzenes, i.e., monochlorobenzene (MCB), p-dichlorobenzene (p-DCB), 1, 3, 5-trichlorobenzene (1, 3, 5-TRCB), 1, 2, 4, 5-tetrachlorobenzene (1, 2, 4, 5-TECB), pentachlorobenzene (PECB) and hexachlorobenzene (HCB). 1) The content of cytochrome P-450 and activities of aminopyrine demethylase and aniline hydroxylase were increased by oral administration of all chlorobenzenes except MCB at daily dose of 250 mg/kg, once daily, for 3 days. The contents of microsomal protein and phospholipids also showed a similar tendency to those as described above. The activity of δ-ALA synthetase was increased by treatment with all compounds used. 2) The content of cytochrome P-450 and activity of aminopyrine demethylase were decreased in 24 hr after a single administration of MCB in doses of 125, 250, 500 and 1000 mg/kg, whereas the activity of δ-ALA synthetase was increased markedly by all doses used. The activity of aniline hydroxylase was increased by a dosing of 1000 mg/kg MCB. 3) In the time-course after a single administration of MCB in a dose of 250 mg/kg, the activity of δ-ALA synthetase was decreased in 6 hr after administration, and subsequently restored to normal levels in 12 hr, and then increased markedly in 24 hr. The opposite changes were noted in the content of cytochrome P-450.