Increased manganese superoxide dismutase activity, protein, and mRNA levels and concurrent induction of tumor necrosis factor alpha in radiation-initiated Syrian hamster cells.
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 of 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 factor alpha (TNF alpha) in HDR-3 cells relative to mock-irradiated cells. Together with the observation that TNF alpha 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 TNF alpha, to which the cells respond by increasing the concentration of Mn-SOD mRNA and protein and the activity of the enzyme.
Otero
G
G
Department of Radiation Medicine, Georgetown University Medical Center, Washington, District of Columbia 20007, USA.
Avila
M A
MA
Emfietzoglou
D
D
Clerch
L B
LB
Massaro
D
D
Notario
V
V
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000528:radiation effects*; D002478:Cells, Cultured; D006224:Cricetinae; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000378:metabolism* / Q000528:radiation effects*; D008647:Mesocricetus; D008928:Mitochondria / Q000378:metabolism / Q000528:radiation effects; D012333:RNA, Messenger / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015854:Up-Regulation / Q000528:radiation effects
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013482:Superoxide Dismutase