Chemical Protection Against Ionizing Radiation

Abstract

Recent work on chemical protection against radiation effects in mammals is reviewed, especially with respect to whole-body exposure to external radiation.This survey shows that many explanations are being offered to account for the action of radioprotective agents. In general, the proposed mechanisms are concerned with inactivation of radicals and other chemical intermediates, depletion of oxygen, or alteration of target molecules. The tendency to interpret protection as a simple competition with free radicals derived from irradiated water has been decreasing in recent years. This is due, in part, to the fact that some agents can protect nonaqueous systems, while others have strong pharmacological properties related to the protective effect. Arguments continue to be advanced for and against a connection between protection by aminothiols and hypoxia, but there is practically no information about intracellular oxygen tensions, a parameter that might give a definitive answer to this question. Various data support the conclusion that some factor other than hypoxia is responsible for the protective action. Even if some protective agents, particularly the biological amines, act by inducing a hypoxia in critical sites, it is still necessary to explain the oxygen effect. The sensitizing action of oxygen has been thought of in terms ofmore » interactions between oxygen molecules and the electrons, ionized and excited molecules, and free radicals that are found along the tracks of ionizing particles. It is suggested that interaction of oxygen with free radicals may lead to the formation of more toxic agents; oxygen interaction with ionized or excited molecules may also provoke their further breakdown. There is also the possibility that protective agents might combine with target molecules and thereby alter their sensitivity; the concept of protection by mixed disulfide formation is an example. It is concluded that a protective agent should be nontoxic with no delayed or cumulative effect, and with a relatively long duration of protective activity. The ideal radioprotectant could be conceived as a ubiquitously distributed energy trap, capable of absorbing and dissipating incident energy without damage to important biological molecules. How such a reactive entity could retain its integrity for long periods of time in the metabolically active cell is difficult to envisage, but if it were possible, protection might far exceed the factor of two in dose reduction which appears now to be the max efficiency for known agents.« less