MAMMALIAN-CELL STUDIES WITH DIAMIDE

Diamide, diazenedicarboxylic acid bis (N,N′-dimethylamide), is a glutathione oxidant that has several advantages over classical sulfhydryl reagents, including reversibility. It is used widely to study glutathione's role in cellular function and radioresistance. It is also an effective radiosensitizer of hypoxic cells and acts by a unique mechanismm increasing the slope of the survival curve of irradiated hypoxic mammalian cells at high concentrations and decreasing the shoulder at low concentrations. Increased yields of radiation-induced chromosome aberrations and DNA strand breaks suggest that diamide sensitizes by mechanisms involving DNA. These mechanisms may include direct interactions with DNA and removal of cellular reducing species that normally repair radiation damage. Diamide sensitizes hypoxic cells synergistically with nitrofuran or nitroimidazole sensitizers, is effective against ascites tumors in vitro, and is useful for elucidating the mechanisms of aminothiol radioprotection. If used carefully, and with due regard for its limitations, it provides a useful tool with which to expand our knowledge of the mechanisms that govern cellular radiosensitivity and to hasten development of effective radiosensitizers for clinical use. © 1979.