Relationship between Chemical Structure and Activity. II. Influences of Isomers in Dichlorobenzene, Trichlorobenzene, and Tetrachlorobenzene on the Activities of Drug-Metabolizing Enzymes

Hepatic constituents and the cytochrome contents in addition to activities of drugmetabolizing enzymes and δ-aminolevulinic acid (δ-ALA) synthetase were examined in rats treated with each isomer of dichlorobenzene (DCB), trichlorobenzene (TRCB) and tetrachlorobenzene (TECB) in an oral dose of 250 mg/kg once daily for 3 days. 1) In the studies on DCB-isomers, activities of aminopyrine demethylase and aniline hydroxylase were enhanced markedly by treatment with m-DCB, whereas cytochrome content was not altered significantly by treatment with any DCB-isomers. δ-ALA synthetase activity was enhanced 63, 32 and 42% by treatment with o-, m- and p-DCB, respectively, but these enhancement were not paralleled with the changes in cytochrome P-450 content. 2) In the administration of TRCB-isomers, enzyme activities were enhanced markedly by treatment with 1, 2, 4-TRCB. Cytochrome P-450 content was also increased by treatment with 1, 2, 4-TRCB, and this increase could be partly related with the enhancement of δ-ALA synthetase activity. 3) By treatment with all TECB-isomers, activity of aminopyrine demethylase was enhanced, whereas aniline hydroxylase was not altered. Cytochrome P-450 content was increased by treatment with all TECB-isomers. 4) Microsomal protein content was increased with all isomers of DCB, TRCB and TECB treatment. Microsomal Pi was increased markedly 36, 70 and 91% by treatment with m-DCB, 1, 2, 4-TRCB and 1, 2, 3, 5-TECB, respectively. Hepatic glycogen content was decreased only by 1, 2, 3, 5-TECB, but triglyceride content was not altered. 5) The spectral change induced by substrate-cytochrome P-450 binding was characterized by type I in each treatment, but conversion of the type occurred in treatment with 1, 2, 4, 5-TECB in high concentration of 1 mM.