Hypoxic mammalian cell radiosensitization by nitric oxide.
The bioregulatory molecule, nitric oxide (NO), was evaluated as a hypoxic cell radiosensitizer. Authentic NO gas was nearly as effective as oxygen in radiosensitizing hypoxic Chinese hamster V79 lung cells as evaluated using clonogenic assays. When NO was delivered to hypoxic Chinese hamster V79 cells using the NO-releasing agent (C2H5)2N[N(O)-NO]- Na+, radiosensitization was also observed with a sensitizer enhancement ratio of 2.4 (1 mM (C2H5)2N[N(O)NO]-Na+). Aerobic radiosensitivity was not affected at this concentration. The hypoxic cell radiosensitization properties of (C2H5)2N[N(O)NO]-Na+, coupled with the vasodilatory effects of NO on tumor vasculature, suggest that such agents open a new avenue of research in radiation oncology.
Mitchell
J B
JB
Radiation Biology Section, National Cancer Institute, Bethesda, Maryland 20892.
Wink
D A
DA
DeGraff
W
W
Gamson
J
J
Keefer
L K
LK
Krishna
M C
MC
D000818:Animals; D015687:Cell Hypoxia; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004048:Diethylamines / Q000032:analysis; D006834:Hydrazines / Q000494:pharmacology*; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009369:Neoplasms / Q000098:blood supply; D009569:Nitric Oxide / Q000494:pharmacology*; D009589:Nitrogen Oxides; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D004048:Diethylamines; D006834:Hydrazines; D009589:Nitrogen Oxides; D011838:Radiation-Sensitizing Agents; D009569:Nitric Oxide; C002385:linsidomine; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; C034281:diethylamine; D008981:Molsidomine