Investigations of the carcinogenic response of laboratory animals to ionizing radiation, either externally or internally applied, are usually focused upon the neoplasms present at death. Consequently the morbidity data are very closely bound to the mortality data, an association that is often overlooked. However, an appreciation of the fact that the true incidence of a disease may be quite different from its apparent incidence at death does not automatically solve the problem of separating morbidity from mortality, because in most instances the recognition of neoplastic disease must wait until the mass can be palpated, or until necropsy. A notable exception is the malignant bone lesion, which can be detected roentgeno-graphically in the living animal long before it can be palpated. The objectives of the present investigation, employing periodic x-ray examination of the skeletons of mice that had received radiostrontium, were: (a) to study the development of osteosarcoma as a disease apart from mortality, (b) to follow the growth of individual tumors from their first roentgenographic identification to the death of the host, and (c) to compare the radiocarcinogenic responses of two distinct strains of mice. Each of these aspects of the investigation is pertinent to the problem of latent period, which is one of the very intriguing but poorly understood characteristics of tumor induction. Materials and Methods Sr90, in equilibrium with Y90, was injected intravenously into 29 CF1 and 24 CBA female mice approximately seventy days old. The former received an average of 0.9 μc/gm. body weight (range, 0.81 to 1.03 μc/gm.) and the latter an average of l.lμc/gm. (range, 0.96 to 1.23 μc/gm.). This amount of Sr90 is known to produce a high incidence of osteosarcoma (1). Roentgenograms were taken one month after injection, at two- to four-week intervals during the next two months, and weekly thereafter. The final picture was obtained at autopsy. Exposure required three-quarters of a second at 30 ma and 32 kv 19 inches from the tube. The radiation received by the mice from this procedure was insignificant compared with that derived from the Sr90-Y90. By retrospective examination of the roentgenograms, the sarcomas present at death could be traced back to their first appearance. It was sometimes difficult to determine the earliest film of a specific lesion with definite neoplastic characteristics, and some lesions persisted in an apparent nonmalignant state for many weeks. If the integrity of the cortex was interrupted, malignancy was diagnosed. In a few instances the cortex was intact, but the general appearance of the lesion favored a diagnosis of malignancy.
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