Lethal Dose Studies with X-Rays

Abstract

I. Introduction Biological evaluation is as indispensable in study of the therapeutic potentiality of radiations as in that of drugs, hormones, or vitamins. This is particularly true of radiations of short wave length, such as x-rays, which are known to produce permanent and irreversible changes. It is well known that there are two fundamentals upon which the evaluation of any therapeutic agent is based (Sollmann, 4): its local action and its toxicity when applied to the entire animal. Studies of the latter type are also called lethal dose studies. In the case of x-rays, relatively satisfactory data are available concerning the local action on various tissues and in different animal species (Ellinger, 2). No such facts have been established, however, for the toxicity of x-rays in general body irradiation. The literature, it is true, contains scattered references to the lethal effect of whole body irradiation for a variety of animals, but most of these data have been obtained under conditions which preclude any accurate evaluation of the results. A systematic study of lethal doses of x-rays seems, therefore, to be desirable from several points of view. In the first place, investigation along this line promises a better understanding of some of the already known effects of x-rays. This may well lead to improvement in the application of radiation therapy and may even open new fields for this form of treatment. In the second place, such studies may furnish data upon which to base a more effective treatment of generalized malignant growth, with less accompanying toxemia. Finally, a more detailed knowledge of lethal doses of x-rays will be of value in the use of artificial radioactive substances as therapeutic agents. The main purpose of lethal dose studies with x-rays is, therefore, (1) to establish lethal doses for various animal species under well defined conditions of irradiation, which will make the data thus obtained generally applicable; (2) if at all possible, to relate lethal doses to body weight or body volume or, if there is no such relationship, to consider the problem of species specificity; (3) to establish the percentage of the lethal dose necessary to produce destructive effects on organs and tumors for various animal species; (4) to establish correlation factors applicable to man, on the basis of lethal doses for animals. The terms “lethal dose” and “sublethal dose” have been used in experimental studies on the effects of radiation with a great variety of meanings. As used throughout our investigations, “sublethal dose” designates any amount of radiation producing no mortality within a given period of time, while “lethal dose” designates any amount of radiation producing a certain percentage of fatalities within a given period of time. It is obvious that without the inclusion of a time factor these terms are meaningless.