2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced lipid peroxidation in genetically responsive and non-responsive mice

Abstract

The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) administration on lipid peroxidation in various strains of responsive and non-responsive mice was determined. The hepatic content of thiobarbituric acid reactive substances (TBARS) was used as an index of lipid peroxidation, employing malondialdehyde as the standard. Six days after the administration of a single oral dose of 0.5 μg TCDD/kg to congenic male C57BL/6J mice, which were either homozygous (bb) or heterozygous (bd) with respect to the gene for the Ah locus, significant increases in hepatic lipid peroxidation were induced. Hepatic lipid peroxidation was induced in homozygous non-responsive (dd) mice by a dose of 25 μg TCDD /kg but not 0.5 μg/kg. In kidney, heart and testis, lower doses of TCDD produced lipid peroxidation in C57BL/6J bb and bd mice as compared to dd mice. The ability of TCDD to induce lipid peroxidation in B6D2F1/J, DBA2J and Swiss-Webster mice was also examined. A dose of 2,500 μg TCDD/kg produced the same level of lipid peroxidation in DBA/2J mice that was observed with 180 μg TCDD/kg in C57BL/6J bb and B6D2F1/J mice. Lipid peroxidation was not induced in kidney, heart, or testis at any of the doses of TCDD that were administered to DBA/2J mice. Thus, large strain differences exist in the ability of TCDD to induce lipid peroxidation in mice. In the liver, the ability to induce lipid peroxidation by TCDD is controlled in part by the Ah “b” allele, although other loci may play a major role.