2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced lipid peroxidation in genetically responsive and non-responsive mice
- 43 Downloads
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.
Unable to display preview. Download preview PDF.
- Birnbaum LS (1986) Distribution and excretion of 2,3,7,8-tetrachlorodibenzo-p-dioxin in congenic strains of mice which differ at the Ah locus. Drug Metab Distrib 14:34–40Google Scholar
- Nebert DW (1981) Genetic differences in susceptibility to chemically-induced myelotoxicity and leukemia. Environ Hlth Persp 39:11–22Google Scholar
- Poland A, and Glover E. (1975) Genetic expression of aryl hydrocarbon hydroxygenase by 2,3,7,8-tetrachiorodibenzo-pdioxin: Evidence for a receptor mutation in genetically nonresponsive mice. Mol Pharmacol 11:389–398Google Scholar
- Poland A, Knutson, JC (1982) 2,3,7,8-tetrachlorodibenzo-pdioxin and related halogenated aromatic hydrocarbons: Examination of the mechanism of toxicity. Pharmacol Toxicol 22:517–554Google Scholar
- Safe SH (1986) Comparative toxicology and mechanism of action of polychlorinated dibenzo-p-dioxins and dibenzofurans. Ann Rev Pharmacol Toxicol 26:371–399Google Scholar