Effects of cellular non-protein sulfhydryl depletion in radiation induced oncogenic transformation and genotoxicity in mouse C3H 10T1/2 cells.

A study was made of the effects of cellular non-protein sulfhydryl (NPSH) depletion on cytotoxicity, cell cycle kinetics, oncogenic transformation and sister chromatid exchange (SCE) in C3H 10T1/2 cells. Using DL-Buthionine S-R-Sulfoximine (BSO) at a concentration of 0.05 mM to deplete thiols, it was found spectrophotometrically that less than 5% of control NPSH level remained in the cells after 24-hour treatment under aerated conditions. Such NPSH depleted cells, when subject to a 3 Gy gamma-ray treatment, were found to have no radiosensitizing response either in terms of cell survival or oncogenic transformation. In addition, decreased levels of NPSH had no effect on spontaneous or radiation-induced SCE nor were cell cycle kinetics additionally altered. Therefore, the inability of NPSH depletion to alter gamma-ray induced cellular transformation was unrelated to any possible effect of BSO on the cell cycle. These results suggest that, while endogenous NPSH depletion has been considered to play an important role for most radiosensitizers in clinical or preclinical use, such depletion may result in little or no additional oncogenic or genotoxic effects on aerated normal tissues.