Induction of oxidative stress and oxidative damage in rat glial cells by acrylonitrile

Chronic treatment of rats with acrylonitrile (ACN) resulted in a dose-relat ed increase in glial cell tumors (astrocytomas). While the exact mechanism( s) for ACN-induced carcinogenicity remains unresolved, non-genotoxic and po ssibly tumor promotion modes of action appear to be involved in the inducti on of glial tumors. Recent studies have shown that ACN induced oxidative st ress selectively in rat brain in a dose-responsive manner. The present stud y examined the ability of ACN to induce oxidative stress in a rat glial cel l line, a target tissue, and in cultured rat hepatocytes, a non-target tiss ue of ACN carcinogenicity, Glial cells and hepatocytes were treated for 1, 4 and 24 h with sublethal concentrations of ACN, ACN induced an increase in oxidative DNA damage, as evidenced by increased production of 8-hydroxy-2' -deoxyguanosine (8-OH-dG) in glial cells but not in rat hepatocytes. Hydrox yl radical formation following ACN treatment was also selectively increased in glial cells. Following 1 and 4 h of ACN exposure, the levels of the non -enzymatic antioxidant glutathione, as well as the activities of the enzyma tic antioxidants catalase and superoxide dismutase were significantly decre ased in the rat glial cells. Lipid peroxidation and the activity of glutath ione peroxidase were not affected by ACN treatment in rat glial cells. No c hanges in any of these biomarkers of oxidative stress were observed in hepa tocytes treated with ACN, These data indicate that ACN selectively induced oxidative stress in rat glial cells.