U.S. Environmental Protection Agency


Date of this Version



Published in TOXICOLOGICAL SCIENCES 42, 23-27 (1998).


The ability of single doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to induce oxidative stress in hepatic and some extrahepatic tissues of animals is well documented. However, no previous study has examined 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 were euthanized 3 days after the last treatment and brain tissues were collected. Biomarkers of oxidative stress including production of superoxide anion, lipid peroxidation, and DNA-single-strand breaks (SSB) were determined. TCDD treatment resulted in significant and dose-dependent increases in the production of superoxide anion as assessed by reduction of cytochrome c. Significant increases were also observed in lipid peroxidation and DNA-SSB in those tissues, as assessed by the presence of thiobarbituric acid-reactive substances and the alkaline elution technique, respectively. These results clearly indicate that subchronic exposure to low doses of TCDD can induce oxidative tissue damage in brain tissues which may at least in part play a role in the effects of TCDD on the central nervous system,