RADIATION SENSITIZATION BY NITRIC-OXIDE RELEASING AGENTS

Previous studies have shown that nitric oxide (NO) sensitises hypoxic cells to ionising radiation. In the present study, four different nitr ic oxide (NO) donor agents were evaluated for both NO release and hypo xic radiosensitisation. The S-nitrosothiol NO donor agents, S-nitrosog lutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP), were sho wn to release sustained NO concentrations (mu M) and significantly rad iosensitise hypoxic cells. The extent of hypoxic radiosensitisation by both of these agents at 1.0 mM concentration was similar to that obta ined with molecular oxygen. In contrast, neither 3-morpholino-sydnonim ine (SIN-1) nor sodium nitroprusside (SNP) released detectable NO conc entrations and neither agent enhanced the hypoxic radiation response t o the extent of that observed for GSNO or SNAP. NO-mediated hypoxic ce ll radiosensitisation by NO donor drugs may offer a new approach for c linical consideration, particularly if such agents can be selectively delivered to hypoxic cells.