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Radiosensitization of hypoxic mammalian cells by diamide. II. Studies of mechanism. [X Radiation]

Journal Article · · Radiat. Res.; (United States)
DOI:https://doi.org/10.2307/3574648· OSTI ID:5112759
Diamide (diazenedicarboxylic acid bis(N,N'-dimethylamide)) radiosensitizes hypoxic Chinese hamster cells by decreasing the shoulder of the survival curve (at low concentrations) and increasing the slope (at high concentrations). We studied the mechanisms responsible for these two phenomena by irradiating cells under different conditions of temperature and substrate availability and measuring either their survival or DNA damage (chromosome aberrations and strand breaks). The results confirm that different mechanisms are responsible for the two effects. The effect on the shoulder appeared to be due to oxidation of endogenous nonprotein sulfhydryls and reduced pyridine nucleotides, compounds that would normally effect rapid chemical repair of certain (single-hit type) lesions. The slope effect, on the other hand, may have been due to reactions with DNA similar to those that have been described for the electron-affinic compounds. These results, together with the finding that hypoxic cells remained sensitized after the removal of diamide when they were irradiated in the cold, provide a useful model and a new experimental approach to the question of chemical radiosensitization.
Research Organization:
Univ. of California, San Francisco
OSTI ID:
5112759
Journal Information:
Radiat. Res.; (United States), Journal Name: Radiat. Res.; (United States) Vol. 70:3; ISSN RAREA
Country of Publication:
United States
Language:
English