Increased manganese superoxide dismutase activity, protein, and mRNA levels and concurrent induction of tumor necrosis factor α in radiation-initiated Syrian hamster cells

✍ Scribed by Gabriel Otero; Matías A. Avila; Dimitris Emfietzoglou; Linda B. Clerch; Donald Massaro; Vicente Notario

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 798 KB
• Volume: 17
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/(sici)1098-2744(199612)17:4<175::aid-mc1>3.0.co;2-d

✦ Synopsis

The levels of the antioxidant enzyme manganese superoxide dismutase (Mn-SOD) are frequently decreased in tumor cells and increased in normal cells upon treatment with ionizing radiation. We studied Mn-SOD at different stages during the neoplastic conversion of radiation-initiated Syrian hamster embryo HDR-3 cells. Mn-SOD activity and the concentration of Mn-SOD protein and mRNA increased gradually during the malignant transformation of HDR-3 cells after radiation exposure; fully neoplastic cells showed greater Mn-SOD levels than preneoplastic and normal 84-3 cells. inhibitors o f superoxide (SO) anion production (thenoyltrifluoroacetone and rotenone) decreased the concentration of Mn-SOD mRNA, raising the possibility that the generation of SO radicals participated in the upregulation of Mn-SOD in cells transformed by exposure to radiation. We observed an increase in the concentration of tumor necrosis factora (TNFa) in HDR-3 cells relative to mock-irradiated cells. Together with the observation that TNFa stimulates the production of SO by mitochondria and increases the level of Mn-SOD mRNA in other experimental systems, our results suggest that as normal 84-3 cells undergo malignant transformation induced by ionizing radiation they produce TNFa, to which the cells respond by increasing the concentration of Mn-SOD mRNA and protein and the activity of the enzyme. o 1% Wiley-Liss. IK