Production of superoxide anion, lipid peroxidation and DNA damage in the hepatic and brain tissues of rats after subchronic exposure to mixtures of TCDD and its congeners

In this study the induction of oxidative stress in the hepatic and brain ti ssues of rats after subchronic exposure to various mixtures of 2,3,7,8-tetr achlorodibenzo-beta -dioxin (TCDD) and two of its congeners, namely 2,3,4,7 ,8-pentachlorndibenzofuran (PeCDF) and 3,3 ' ,4,4 ' ,5-pentachlorobiphenyl (PCB 126) was investigated. Four mixtures of TCDD and its congeners, corres ponding to 10, 22, 46 and 100 ng of toxic equivalence (TEQ) kg(-1) day(-1), were administered to groups of rats for 13 weeks. The animals were sacrifi ced at the end of the exposure period and the biomarkers of oxidative stres s, including the production of superoxide anion, lipid peroxidation and DNA single-strand breaks (SSBs), were determined in the hepatic and brain tiss ues. All mixtures caused dose-dependent increases in the production of supe roxide anion, lipid peroxidation and DNA SSBs in both tissues, with signifi cantly higher damage in the hepatic compared with the brain tissues. The 22 ng TEQ dose level (TEQ = 22) contains TCDD, PeCDF and PCB 126 at Levels th at correspond to 7,3, 14.5 and 73.3 ng kg(-1) day(-1), respectively, and it produced effects that correspond to ca, 50% of the maximal production of s uperoxide anion, lipid peroxidation and DNA SSBs in the hepatic and brain t issues of those animals. Relative to the doses that are required to produce 50% of the maximal production of the biomarkers of oxidative stress by the individual congeners in hepatic and brain tissues of rats, the concentrati ons of the congeners in TEQ = 22 did result in significant interactivity, p robably in the form of additive effects in the hepatic but not in brain tis sues. Copyright (C) 2001 John Wiley & Sons, Ltd.