Induction of oxidative stress and oxidative damage in rat glial cells by acrylonitrile.
Chronic treatment of rats with acrylonitrile (ACN) resulted in a dose-related increase in glial cell tumors (astrocytomas). While the exact mechanism(s) for ACN-induced carcinogenicity remains unresolved, non-genotoxic and possibly tumor promotion modes of action appear to be involved in the induction of glial tumors. Recent studies have shown that ACN induced oxidative stress selectively in rat brain in a dose-responsive manner. The present study examined the ability of ACN to induce oxidative stress in a rat glial cell line, a target tissue, and in cultured rat hepatocytes, a non-target tissue 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. Hydroxyl 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 enzymatic antioxidants catalase and superoxide dismutase were significantly decreased in the rat glial cells. Lipid peroxidation and the activity of glutathione peroxidase were not affected by ACN treatment in rat glial cells. No changes in any of these biomarkers of oxidative stress were observed in hepatocytes treated with ACN. These data indicate that ACN selectively induced oxidative stress in rat glial cells.
Kamendulis
L M
LM
Division of Toxicology, Department of Pharmacology and Toxicology, Indiana University School of Medicine, 635 Barnhill Drive, MS 1021, Indianapolis, IN 46202-5120, USA.
Jiang
J
J
Xu
Y
Y
Klaunig
J E
JE
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000181:Acrylonitrile / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D002273:Carcinogens; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D003849:Deoxyguanosine; D000181:Acrylonitrile