Cytotoxicity and manganese superoxide dismutase induction by tumor necrosis factor-alpha and ionizing radiation in MCF-7 human breast carcinoma cells.

Both tumor necrosis factor-alpha (TNF) and ionizing radiation cause active-oxygen radical-mediated cell injuries and cell death. Thus cells treated by both TNF and radiation may suffer greater injuries than cells treated by either agent alone. On the other hand, TNF or radiation treatment can stimulate the expression of a mitochondrial superoxide scavenging enzyme, manganese superoxide dismutase (MnSOD), which can lower the cytotoxic effects of both agents. Thus, the induction of MnSOD by radiation may interfere with the cytotoxic action of TNF and vice versa. We used a human breast tumor cell line, MCF-7, to determine the interaction of TNF and radiation on cytotoxicity and MnSOD expression. TNF was found to be more effective as a cytotoxic agent when used before than after radiation treatment. These observations suggest that radiation induced-MnSOD was more effective in reducing the cytotoxic effect of TNF whereas TNF induction of MnSOD was less effective in counteracting the radiation action. Our results not only underscore the different effects of the treatment order of TNF and radiation, but also point to potential implication in the radiotherapy of breast tumors.