Polyfunctional Radiosensitizers: II. Interaction of the Biradical (Ro 03-6061) with Reducing Species

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Abstract
Preincubation of the biradical Ro 03-6061 (nitroxyl) with human erythrocytes rendered the molecule ineffective as a sensitizer of hypoxic V79 [Chinese hamster lung] cells. The rate of reduction of the biradical with reduced glutathione proceeded much more slowly than that of the monoradical nitroxyl NPPN [nor-pseudopelletierine-N-oxyl] and the reaction was faster at 37.degree. C than at room temperature. The reduction of the free radical centers was reflected in its radiosensitizing ability, causing changes in the survival curves of hypoxic V79 cells with respect to both DO and the extrapolation number. The efficacy of the biradical as a sensitizer was not completely removed by treatment with reduced glutathione at 37.degree. C whereas there was no sensitization of hypoxic cells in the presence of NPPN that had been pretreated similarly with reduced glutathione. The results are discussed in terms of the chemistry of the molecule and possible mechanistic differences between mono- and biradical nitroxyls and other shoulder-modifying sensitizers such as diamide.