SELECTIVE TOXICITY OF BUTHIONINE SULFOXIMINE (BSO) TO MELANOMA-CELLS IN-VITRO AND IN-VIVO

Purpose: Glutathione (GSH) was found to occur in relatively high conce ntrations in melanoma cells. The purpose of this study was to test the possible cytotoxic effects of an artificial decrease of the elevated GSH level. Methods and Materials: The tests were made in vitro and in vivo. In the former case, a total of II rodent and human cell lines we re studied of which seven were derived from melanomas. After treatment with buthionine sulfoximine (BSO), the decrease of GSH content of the cells and their clonogenic survival was determined. In the in vivo sy stem, single cell suspensions of a subline of the B16 mouse melanoma w ere injected intravenously into immunocompetent and preirradiated reci pients which were subsequently treated with BSO intraperitoneally. Sur vival time, formation of lung colonies and the weight of metastatic tu mor mass in the lungs were the criteria of the BSO effect on the tumor cells. Results: The decrease of the GSH level by BSO was associated w ith impaired clonogenic survival of the melanoma cells in vitro. Nonme lanoma cells were less affected. BSO treatment of mice inoculated intr avenously with melanoma cells resulted in prolonged survival of the an imals and impaired metastatic spread of the tumor cells. Conclusion: M elanoma cells are particularly sensitive to disturbance of GSH metabol ism by treatment with BSO. In view of this selective cytotoxicity of B SO, treatment with this substance may afford a promising therapeutic p otential for melanoma.