INDUCTION OF OXIDATIVE STRESS IN BRAIN-TISSUES OF MICE AFTER SUBCHRONIC EXPOSURE TO 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN

The ability of single doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TC DD) to induce oxidative stress in hepatic and some extrahepatic tissue s of animals is well documented. However, no previous study has examin ed the ability of TCDD to induce oxidative stress and tissue damage in brain in vivo. In this study the ability of TCDD to induce oxidative stress in brain tissues of mice was studied after subchronic exposures . Groups of female B6C3F1 mice were treated orally with TCDD (0, 0.45, 1.5, 15, and 150 ng/kg/day) for 13 weeks, 5 days/week. The animals we re euthanized 3 days after the last treatment and brain tissues were c ollected, Biomarkers of oxidative stress including production of super oxide anion, lipid peroxidation, and DNA-single-strand breaks (SSB) we re determined. TCDD treatment resulted in significant and dose-depende nt increases in the production of superoxide anion as assessed by redu ction of cytochrome c. Significant increases were also observed in lip id peroxidation and DNA-SSB in those tissues, as assessed by the prese nce of thiobarbituric acid-reactive substances and the alkaline elutio n technique, respectively. These results clearly indicate that subchro nic exposure to low doses of TCDD can induce oxidative tissue damage i n brain tissues which may at least in part play a role in the effects of TCDD on the central nervous system. (C) 1998 Society of Toxicology.