Oxidative stress in female B6C3F1 mice following acute and subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a highly persistent trace env ironmental contaminant and is one of the most potent toxicants known to man . Hassoun et al, (1998, Toxicol. Sci. 42, 23-27) reported an increase in th e production of reactive oxygen species (ROS) in the brain of female B6C3F1 mice following subchronic exposure to TCDD at doses as low as 0.45 ng/kg/d ay. In the present study, oxidative stress was characterized in liver, sple en, lung, and kidney following subchronic (0.15-150 ng/kg; 5 days/week for 13 weeks, po) or acute exposure (0.001-100 mu g/kg, po) to TCDD in order to investigate the interaction between tissue concentration and time for prod uction of ROS. Seven days following acute administration of TCDD, mice were sacrificed; they demonstrated increases in liver superoxide anion producti on (SOAP) and thiobarbituric acid reactive substances (TBARS) at doses of 1 0 and 100 mu g/kg, associated with hepatic TCDD concentrations of 55 and 32 1 ng/g, respectively, Liver obtained from mice following subchronic TCDD ex posure demonstrated an increase in SOAP and TBARS above controls at doses o f 150 ng/kg/day with liver TCDD concentration of only 12 ng/g. Interestingl y, glutathione (GSH) levels in lung and kidney following subchronic TCDD ex posure were decreased at the low dose of 0.15 ng/kg/day. This effect disapp eared at higher TCDD doses. The data suggest that higher tissue TCDD concen trations are required to elicit oxidative stress following acute dosing tha n with subchronic TCDD exposure. Therefore, the mechanism of ROS production following TCDD exposure does not appear to be solely dependent upon the co ncentration of TCDD within the tissue. In addition, very low doses of TCDD that result in tissue concentrations similar to the background levels found in the human population produced an effect on an oxidative stress endogeno us defense system, The role of this effect in TCDD-mediated toxicity is not known and warrants further investigation.