Polyfunctional Radiosensitizers III, Effect of the Biradical (Ro-03-6061) in Combination with Other Radiosensitizers on the Survival of Hypoxic V-79 Cells

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Abstract
The biradical Ro-03-6061 [bis(2,2,6,6-tetramethyl-1-oxyl-4-piperidinyl) succinate] removes the shoulder from the survival curve of hypoxic V-79 [Chinese hamster lung cells] whereas both NPPN [norpseudopelletierine-N-oxyl] and PNAP [p-nitroacetophenone] are dose-modifying sensitizers like O2. When hypoxic cells were irradiated in the presence of a combination of NPPN and the biradical at equivalent radical concentrations, the survival curve was similar to that for cells irradiated in the presence of NPPN alone. When a combination of PNAP and the biradical were used at a concentration where the number of electron affinic (PNAP) molecules was equal to the number of free radical moieties, the resultant DO [lethal dose] value was similar to that for PNAP alone but the shoulder of the curve was not completely restored. In experiments where the biradical was used in combination with diamide the effect was additive. Cell kill was exponential even at low doses when 0.05 mM diamide was used in combination with 0.1 mM biradical; the extrapolation number was 1.0 and the DO was 240 rad. The results suggest mechanistic differences between electron affinic, free radical and sulfhydryl-binding radiosensitizers, and also differences between monofunctional and polyfunctional sensitizers.

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