DIP and DIP+2 as glutathione oxidants and radiation sensitizers in cultured Chinese hamster cells.

Abstract

Two diamide analogues, diazene dicarboxylic acid bis (n'-methylpiperazide) or DIP, and its bis-N'-methyl iodide salt, or DIP + 2, were tested for their ability to penetrate cultured Chinese hamster cells and oxidize intracellular glutathione. DIP penetrated the cells at a reasonable rate at 18 degrees C, 160 nmoles being required to oxidize the endogenous glutathione of 2 X 10(6) cells, but it penetrated very slowly at 0 degrees C. DIP +2 did not effectively oxidize glutathione in Chinese hamster cells, possibly because it did not enter the cells. DIP became toxic after about 10 min of exposure, but its toxicity could be moderated by using anoxic conditions. DIP, but not DIP +2, sensitized anoxic Chinese hamster cells to X-radiation by a factor of 1-5, an effect that was due entirely to removal of the shoulder from the survival curve.