Protective Action of Anoxic Anoxia Against Total Body Roentgen Irradiation of Mammals

Abstract

A number of experiments have been carried out which indicate that a reduction in oxygen tension reduces irradiation injury in mammals (1, 2, 4), plants (3, 7, 8), yeast (6), and in tissue cultures (5). In mammals, reduced irradiation injury has been demonstrated in cases where the circulation has been impaired (1, 4) by strapping the chests of day-old rats (4), in poorly vascularized tumors (9), and in severe anemia (2). The interpretation and evaluation of each of these experiments are complicated by the presence of several variables. For example, in the experiments in which the circulation of a limb or tail was blocked, other essential metabolites, as well as oxygen, failed to reach the cells. Also, carbon dioxide and other products could not be removed from the cells. In the chest-strapping experiments, the degree of anoxia is unknown, and in the anemia experiments, likewise, secondary responses other than anoxia could have taken place. When all the experiments are considered as a group, however, they have one common factor, namely, reduced oxygen tension. In the plant pollen, tissue culture, and yeast experiments, no circulation is involved. Therefore, anaerobiosis must protect either by its effect on metabolism or by blocking certain radiochemical reactions in which oxygen is necessary. In the studies to be reported here, the effect of extreme anoxic anoxia of brief duration on the LD 50 and on the radiation syndrome observed in mammals after total-body roentgen irradiation has been investigated. By using a brief period of anoxia, it was hoped to avoid any variables caused by the secondary reactions due to anoxia alone. It was observed that anoxia gave a high degree of protection from lethal roentgen irradiation and ameliorated the clinical picture. Materials and Methods In these studies, male and female rats (average weight, 170 gm.) of a Wistar strain were used. The rats were maintained on a diet of Rockland rat chow and given water ad libitum. After irradiation, aureomycin, 25 mg. per cent, was added to the drinking water. Growth curves and clinical appearances were noted for each rat for a period of ten days before irradiation and thirty-five days post irradiation. The rats were irradiated one at a time in an air-tight leucite chamber (10 × 10 × 5 cm.). The gas mixtures from commercial cylinders were bubbled through water and entered the chamber through ¼-inch tubing. The gas escaped from the chamber through a 1-foot length of ¼-inch tubing. The effluent gas was checked for its oxygen content with a Beckman oximeter. The gases were flushed through the chamber for approximately ninety seconds before irradiation to bring about their equilibration and to allow the rats to become anoxic. A continuous flow of gases was maintained during irradiation. The anoxic anoxia rats were irradiated in a mixture of 5 per cent oxygen and 95 per cent nitrogen.