Experimental induction of bone tumors by short-lived bone-seeking radionuclides

Single and repeated applications of 224Ra and single applications of 227Th to more than 600 female NMRI mice 3 - 4 weeks old, and to male NMRI mice have led to a high rate of osteosarcomas. Tumor incidence is dose-related. 227Th is more carcinogenic than 224Ra which induced the highest tumor incidence of 60% after a single injection of 5 muCi per Kg body weight or more. Repeated injections of 224Ra to female mice yielded a tumor incidence of up to 92%. Most of these osteosarcomas consist of well-differentiated bone-forming osteoplastic tissue. Half of the tumors occurred in the spine, particularly in the lumbar region. In protraction experiments, multifocal osteosarcomas have been observed. Less than 10% of the mice with osteosarcoma had developed metastases in lung, spleen, liver, and kidney. The possible mechanisms of the protraction effect are discussed.