Estimation of Prevalence Rates of Radiogenic Leukemias in RFM/U Mice

Murine leukemia can be diagnosed only when the mouse is moribund. Pallor of ears, feet, or nose, ruffled fur, palpable spleen, and shortness of breath indicate terminal leukemia. As a result, no data exist on the prevalence rates of murine leukemias. This lack contrasts strangely with the widespread use of these diseases in experimental cancer research. The morphology of preterminal lesions in irradiated mice has been studied extensively (1), as well as various component processes of the preleukemic state (2); but the available observations do not allow inferences regarding the prevalence rates of overt leukemia. An accidental finding during an earlier experiment with murine leukemia suggested a new approach to this problem. In that experiment (3), we studied correlations between late radiation injury in blood-forming tissues and the percent cumulative probability of leukemia. The latter was determined in groups of mice allowed to live out their natural life span. Out of these groups, clinically nonleukemic mice were randomly selected and sacrificed. Thirty-five of the 296 mice sacrificed revealed early leukemic change when examined histologically, and could not be used for the study of nonmalignant late radiation injury. This finding suggested the design of the experiment described here. A group of several hundred mice received one single leukemogenic X-ray exposure. Starting with Day 70 after irradiation, randomly selected groups of mice were sacrificed at seven preselected time intervals, and examined for early histopathological evidence of leukemia. This enabled us to estimate the point-prevalence rates of leukemia at the time periods selected for sacrifice. Materials and Methods. Mice. A total of 524 mice of both sexes, of the RFM/U strain, were used. At the time of irradiation they were 80–120 days old. The original stock was supplied by Dr. Arthur C. Upton, Biology Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee (now at the Health Sciences Center, University of New York at Stony Brook).