Radiosensitization of hypoxic tumor cells in vitro by nitric oxide.
OBJECTIVE
The effects of nitric oxide (NO) on the radiosensitivity of SCK tumor cells in oxic and hypoxic environments in vitro were studied.


METHODS
NO was delivered to cell suspensions using the NO donors 2,2-diethyl-1-nitroso-oxyhydrazine sodium salt (DEA/NO), and a spermine/nitric oxide complex (SPER/NO), which release NO at half-lives of 2.1 min and 39 min at pH 7.4, respectively. The cells were suspended in media containing DEA/NO or SPER/NO for varying lengths of time under oxic or hypoxic conditions, irradiated, and the clonogenicity determined.


RESULTS
Both compounds markedly radiosensitized the hypoxic cells. The drug enhancement ratios (DER) for 0.1, 1.0, and 2.0 mM DEA/NO were 2.0, 2.3 and 3.0, respectively, and those for 0.1, 1.0, and 2.0 mM SPER/NO were 1.6, 2.3, and 2.8, respectively. Aerobic cells were not radiosensitized by DEA/NO or SPER/NO. When DEA/ NO and SPER/NO were incubated in solution overnight to allow release of NO, they were found to have no radiosensitizing effect under hypoxic or oxic conditions indicating the sensitization by the NO donors was due to the NO molecule released from these drugs. At the higher concentrations, SPER/NO was found to be cytotoxic in aerobic conditions but not in hypoxic conditions. DEA/NO was only slightly toxic to the cells in both aerobic and hypoxic conditions.


CONCLUSIONS
NO released from NO donors DEA/NO and SPER/NO is as effective as oxygen to radiosensitize hypoxic cells in vitro. Its application to the radiosensitization of hypoxic cells in solid tumors remains to be investigated.
University of Minnesota Medical School, Department of Therapeutic Radiology-Radiation Oncology, Minneapolis, MN 55455, USA.
R J
RJ
Griffin
C M
CM
Makepeace
W J
WJ
Hur
C W
CW
Song
D000332:Aerobiosis; D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000532:radiotherapy*; D051379:Mice; D009569:Nitric Oxide / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D011838:Radiation-Sensitizing Agents; D009569:Nitric Oxide