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Increased manganese superoxide dismutase activity, protein, and mRNA levels and concurrent induction of tumor necrosis factor α in radiation‐initiated Syrian hamster cells
Author(s) -
Otero Gabriel,
Avila Matías A.,
Emfietzoglou Dimitris,
Clerch Linda B.,
Massaro Donald,
Notario Vicente
Publication year - 1996
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/(sici)1098-2744(199612)17:4<175::aid-mc1>3.0.co;2-d
Subject(s) - superoxide dismutase , tumor necrosis factor alpha , biology , neoplastic transformation , microbiology and biotechnology , hamster , downregulation and upregulation , superoxide , antioxidant , enzyme , biochemistry , endocrinology , carcinogenesis , gene
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 α (TNFα) in HDR‐3 cells relative to mock‐irradiated cells. Together with the observation that TNFα 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 TNFα, to which the cells respond by increasing the concentration of Mn‐SOD mRNA and protein and the activity of the enzyme. © 1996 Wiley‐Liss, Inc.