In vitro induction of reactive oxygen species by 2,3,7,8-tetrachlorodibenzo-p-dioxin and other halogenated cyclic hydrocarbons in rat peritoneal macrophages, and hepatic mitochondria and microsomes

Abstract

Polyhalogenated cyclichydrocarbons [PCH] including 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD], endrin and lindane [hexachlorocyclohexane] are potent toxins and tumor promoters. Recent studies have shown that these xenobiotics produce an oxidative stress in rodents, and tissue damage produced by these toxins as well as tumor promotion may be related to the formation of reactive oxygen species. In the present study hepatic mitochondria and microsomes as well as peritoneal macrophages from female Sprague-Dawley rats were incubated for up to 45 min at 37° C in the presence of 0–200 ng/ml TCDD, endrin and lindane. Production of reactive oxygen species was determined by chemiluminescence and cytochrome c reduction, while potential tissue damage was assessed by alterations in membrane fluidity and enhanced lipid peroxidation. Under these conditions, the three PCH resulted in enhanced production of reactive oxygen species. Furthermore, enhanced lipid peroxidation of mitochondrial and microsomal membranes was observed with increases in the membrane microviscosity. Thus reactive oxygen species and membrane alterations may contribute to the toxicity of PCH.