Studies on the Radioprotective Action of Sodium Nitrite in Mice

Abstract

Hypoxic mice are protected against certain doses of irradiation regardless of whether hypoxia is induced by an atmosphere of low oxygen or by injection of chemicals. Sodium nitrite and p-aminopropiophenone (PAPP) are among the chemicals thought to exert their protective effect, in part, by hypoxia resulting from severe methemoglobinemia (1, 2). Serotonin, on the other hand, exerts its effect mainly by causing hypoxia through its vasoconstrictive action on the spleen and bone marrow2 (3). To evaluate these and other radioprotective compounds, changes in oxygen tension in the spleen and vena cava of mice were measured polarographically. On the assumption that whole-body irradiation causes death primarily through effects on the hematopoietic system, the degree of hypoxia at the time of irradiation should presumably correlate with the degree of protection. Sodium nitrite was of particular interest because it was possible to administer doses that would reduce the oxygen tension to relatively low levels and then protect the animal against death from nitrite by injecting methylene blue. Radioprotection studies by others have shown that a dose of 100 mg of sodium nitrite per kilogram was totally ineffective against 800 R (1); at doses of 100 to 125 mg/kg the average survivals of the treated mice exposed to 600 R or 750 R were 97 % and 78 %, respectively, and the corresponding survivals of the controls were 19 % and 0 % (2). In another study (4) a dose of 120 mg/kg protected 100 % of the mice against 750 R and an average of 46 % against 900 R, whereas there were no survivors in the untreated groups. The present study was undertaken to determine whether by administering larger doses of sodium nitrite, thereby producing a greater degree of hypoxia, protection against irradiation could be enhanced. Studies were also carried out to investigate