Synergistic lethal action of certain radioisotopes in rats.

Abstract

As is well known, one of the primary factors which determines the nature of the acute toxicity of an internally administered radioactive isotope is its pattern of distribution in the body. For example, the toxicity of P32 in rats is significantly less in the form of colloidal CrPO4 than in the form of ionic Na2HPO4. By using two separate isotopes having widely different distributions, it is possible to study the interrelationship of various systems in the body as well as to elucidate the dependence of survival of the whole organism upon the injury of specific organ systems. Previous studies in this laboratory have shown that a combination of colloidal Au198 and P32 administered to rats is more lethal than either agent administered singly (1). These experiments have been extended to determine whether synergistic lethal action occurs with other internal emitters when these are used in combination. Material and methods P32, obtained from the U. S. Atomic Energy Commission, Oak Ridge, Tenn., was used as Na2HPO4 and in the preparation of colloidal chromic phosphate. The preparation of this colloid was according to the method of Jones, Wrobel and Lyons (2) and is described in detail in a previous report (3). Sr89' 90 was also obtained from the above source and was incorporated into colloidal Sr3(PO4)2 following the procedure of DeToni (4). Colloidal Au198 was obtained from Abbott Laboratories, North Chicago, Ill. The colloidal preparations were injected intravenously into either lateral tail vein of the rat after the animal had been immobilized in a wire cage and the tail washed in tepid water. Volumes of less than 0.5 c.c. were slowly injected with a 26-gauge needle. The incidence of faulty injections was less than 10 per cent, and such animals were immediately discarded from the experiment. Na2HPO4 was always injected intraperitoneally. Other details of procedure were as reported in a previous communication (1). In order to establish reference data for the investigation of the lethal action of two radioisotopes administered simultaneously, determinations were made of the approximate 30-day LD 50 values of each agent. Radiation dosages of all isotopes were on a microcurie per gram of rat basis. The validity of this procedure has been established in this laboratory (3). At least 100 animals were used in each LD 50 determination. The dosage-mortality data are plotted on logarithmic probability paper in Figure 1. Although each isotope was standardized in our laboratory and agreement with other assays was within 5 per cent, the colloidal preparations sometimes deviated significantly from the anticipated lethal potency. This variable was controlled by concomitant testing of each isotope singly with each combination experiment.