A protective role for metallothionein (MT) in cellular injury caused by ionizing radiation has been proposed. To elucidate the role of MT in the sensitivity of tumors to radiation, we examined the effectiveness of radiation treatment of tumors with altered synthesis of MT after injection of tumor-bearing mice with zinc and/or propargyl glycine (PPG). The mice were inoculated with Meth-A fibrosarcoma cells and the antitumor activity of X radiation was tested in mice with and without induced synthesis of MT. Exposure to X radiation decreased the tumor weight markedly. In mice pretreated with zinc to induce MT, the tumor weight did not change compared to the controls. However, injection of PPG, an inhibitor of cystathionase, decreased the zinc-induced MT synthesis in the tumors and also decreased the tumor weight after exposure to X radiation. These results suggest that in radiation therapy one of the factors involved in radiosensitivity may be the expression of MT in certain tumors.

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