Radiation sensitisation 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 nitric oxide (NO) donor agents were evaluated for both NO release and hypoxic radiosensitisation. The S-nitrosothiol NO donor agents, S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylpenicillamine (SNAP), were shown to release sustained NO concentrations (microM) and significantly radiosensitise hypoxic cells. The extent of hypoxic radiosensitisation by both of these agents at 1.0 mM concentration was similar to that obtained with molecular oxygen. In contrast, neither 3-morpholinosydnonimine (SIN-1) nor sodium nitroprusside (SNP) released detectable NO concentrations and neither agent enhanced the hypoxic radiation response to the extent of that observed for GSNO or SNAP. NO-mediated hypoxic cell radiosensitisation by NO donor drugs may offer a new approach for clinical consideration, particularly if such agents can be selectively delivered to hypoxic cells.
Mitchell
J B
JB
Radiation Biology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
Cook
J A
JA
Krishna
M C
MC
DeGraff
W
W
Gamson
J
J
Fisher
J
J
Christodoulou
D
D
Wink
D A
DA
D000818:Animals; D015687:Cell Hypoxia; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D006224:Cricetinae; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D026422:S-Nitrosoglutathione
D009603:Nitroso Compounds; D011838:Radiation-Sensitizing Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D026422:S-Nitrosoglutathione; D005978:Glutathione