Specificity of endogenous glutathione in determining the oxygen enhancement of cellular radiosensitivity.

Oxygen enhancement ratios (OER) determined with single-strand DNA breaks as end-point of radiation effect were lower for cells with genetically determined glutathione (GSH) deficiency, than for cells depleted of GSH artificially to a corresponding degree by treatment with buthionine sulfoximine (BSO). In view of a considerable non-protein thiol (NPSH) accumulation found in both cases, the difference can be attributed to different NPSH components. Those in the BSO-treated cells having the capacity to substitute for GSH in the processes which define OER. As an alternative explanation, the particular location of GSH in GSH-proficient cells in close contact with the critical radiation target can be considered. At these sites, as indicated by measurements of NPSH in isolated nuclei, BSO may not deplete thiols as efficiently as at other sites. Observations on a persisting difference found between the OER of genetically GSH-deficient and proficient cells after treatment with dithiothreitol (DTT) can also be given a spatial explanation, assuming that exogenous thiols may not reach the critical sites in the nucleus in efficient concentrations.