Diamide: A New Radiosensitizer for Anoxic Cells

This study was undertaken to evaluate the effect of the glutathione-oxidizing reagent, diamide, on the radiosensitivity of euoxic and anoxic bacteria (Pseudomonas fluorescens) and Chinese hamster cells (V79, B14FAF, and CHO). Doses of diamide which are just sufficient to oxidize cellular nonprotein sulfhydryl completely do not sensitize euoxic or anoxic mammalian cells to x-rays. Excess reagent, however, sensitizes cells irradiated in nitrogen but not in air. A similar situation is found in P. fluorescens: anoxic cells are sensitized by diamide, whereas the survival of euoxic cells is unaffected by it. Sensitization of anoxic mammalian cells by diamide is unique in that the reagent causes only a small decrease in D₀ (approximately 30%) but completely removes the shoulder of the survival curve-i.e., the extrapolation number is reduced to one. Preliminary results indicate that a combination of diamide and the slope-modifying compound, nifuroxime, sensitizes anoxic V79 cells better than either compound alone and, in fact, better than oxygen. The results are discussed in relation to the role of endogenous nonprotein sulfhydryl in radiation sensitivity and to the possible use of diamide as a radiosensitizer for anoxic tumor cells in vivo.