Myeloid Leukemia in the Mouse

Abstract

Myeloid leukemia, one of the earliest recognized examples of radiogenic cancer (see Furth and Lorenz, 1954), is conspicuously increased in frequency among people surviving high-level, whole-body ionizing irradiation (Brill et al., 1962; Wald et al., 1962). Because of t,he importance of this neoplasm as a radiation hazard, the mechanisms and kinetics of its induction merit systematic investigation. For this purpose, mice of the R F strain are ideally suited, since a large proportion of them develop myeloid leukemia in response to relatively small amounts of whole-body radiation. Observations on the radiologic and host factors influencing the development of the disease in such animals are surveyed in this article.Clinicopathologic features. The myeloid leukemia encountered in irradiated R F mice is indistinguishable from that occurring spontaneously in mice of this and other strains. Clinical, hematologic, and pathologic features have been described elsewhere (see Dunn, 1954;Upton and Furth, 1954; Parsons et aE., 1962). It is noteworthy, however, that the disease closely resembles chronic granulocytic leukemia of man. The leukocytes in the peripheral blood characteristically show a high degree of maturation, and the infiltrations in the marrow, spleen, and liver are exclusively of granulocytes and their precursors. A predominance of myelocytes and more primitive forms is seen only after serial transplantation of the neoplasm. Whether the clinical course of the primary disease is acute or chronic cannot be determined from the information at hand, since its diagnosis has been made ank rnortem only in terminally ill or moribund mice.Incidence in relation to radiation dose. Apart from the influence of host factors, which is mentioned below, the incidence of leukemia at any given dose level varies with the dose rate; the number and frequency of exposures; the linear energy transfer (LET) of the radiation; and the fraction of the body irradiated.When the mice are exposed to whole-body X or y irradiation in a single, brief exposure ($100 rads/min.) early in adult life (five to ten weeks of age), one finds that the incidence is increased several times above normal by a dose of 100 r, reaches maximal levels at 200-400 r, and declines at higher dose levels, the peak response in males (FIGURE la) exceeding that *Operated by Union Carbide Corporation for the United States Atomic Energy Commission. 189

Effects of Dietary Antioxidant Supplementation on the Development of Malignant Lymphoma and Other Neoplastic Lesions in Mice Exposed to Proton or Iron-Ion Radiation

“…Some of the differences in yields of malignant lymphoma in X-and proton-irradiated CBA mice could be due to promotional factors, which were absent in the mice used in this study. It is well known that other factors have a major influence on the development of radiation-induced malignant lymphoma, such as dietary restriction (32,33), hormones (34,35) and exposure of the irradiated animals to turpentine (36), which is considered to be a classic promoting agent for carcinogenesis (37,38). Diet alone is known to have major effects on carcinogenesis.…”

Comparative Risk Predictions of Second Cancers After Carbon-Ion Therapy Versus Proton Therapy

“…Furthermore, the carcinogenesis process may itself exhibit non-linear dose response, as seen clearly in in-vivo experiments, e.g. , induction of tumors in mice [5,44] and seen in in-vitro cell transformation experiments [48]. These findings have inspired the development of nonlinear risk models [39], which have been used to estimate second cancer risks after modern radiotherapy techniques [33].…”

Mouse Models for Efficacy Testing of Agents against Radiation Carcinogenesis — A Literature Review

“…Exposure of 8-week old RF males to 1.5 Gy increases ML frequency to about 40% while in utero and neonatal exposures actually decrease ML induction [29,40]. At the dose of 4.25 Gy ML incidence increases to 50–90%, with a latency period of 4–12 months [30,37,41].…”