Role of intracellular SOD in protecting human leukemic and cancer cells against superoxide and radiation.
Many anticancer drugs have been shown to produce superoxide anion (O2.-) and seem to involve O2.- in their mode of action. Ionizing radiation provokes the decomposition reaction of water, producing a variety of reactive oxygen species, including O2.-. The finding that cancer cells are generally low in SOD activity may offer a theoretical base for radiation therapy and chemotherapy. The purpose of this study was to examine the protective effect of intracellular SOD against cytotoxicity induced by O2.- or radiation and to investigate whether exogenous SOD can protect cells from O2.-(-) and radiation-induced cytotoxicity. For this purpose, xanthine (X) and xanthine oxidase (XOD) were employed as an O2.- (-)generating system, and a linear accelerator was used for ionizing radiation. Cytotoxicity against monolayer cancer cell lines and leukemic cell lines was estimated by measuring the release of lactate dehydrogenase from these cells. The results revealed that the resistibilites to X- and XOD-generated O2.- and radiation correlated with intracellular Cu. Zn-SOD levels and that exogenous SOD could only slightly reduce X- and XOD-induced cytotoxicity while having no influence on radiation-induced cytotoxicity. Thus, intracellular SOD may play a central role in protecting cancer cells against reactive oxygen species generated by anticancer drugs and radiation.
Second Department of Oral and Maxillofacial Surgery, School of Dentistry, Showa University, Tokyo, Japan.
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Yamaguchi
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Sakurada
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Nagumo
D002294:Carcinoma, Squamous Cell; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007770:L-Lactate Dehydrogenase; D007938:Leukemia; D009062:Mouth Neoplasms; D013482:Superoxide Dismutase / Q000378:metabolism*; D013481:Superoxides / Q000633:toxicity*; D014407:Tumor Cells, Cultured; D019820:Xanthine; D014969:Xanthine Oxidase / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D014970:Xanthines; D013481:Superoxides; D019820:Xanthine; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase