Dose Dependence of the Severity of Radiation-Induced Thymic Lymphoma in Mice

The dose dependence of the severity of radiation-induced thymic lymphoma in C57BL/6J mice was studied. Mice were exposed to fractionated irradiation at the total doses of 4.0, 6.0 and 8.0 Gy (four irradiations at 8-day intervals) starting from 33 days after birth. Pathological and histological changes of each mouse were observed after periodical sacrifice at day 75, 100, 125, 150, 175, 200, 250, 300 after the first irradiation. The severity of cancers were classified into 4 stages by clinical signs with respect to the enlargement of the thymus, spleen, liver, the progression of the cancer in the thymus, and the metastasis to the spleen, liver, lung and the lymphatic nodes. Among the 490 mice observed, 146 mice had thymic lymphoma. A clear dose-effect relationship was observed as well as the dose-response relationship. Also, periodical observation showed that thymic lymphoma was first induced in mice sacrificed at day 100 (130days old), and metastasize in the order of spleen, lung, liver and then the lymphatic nodes. The results suggest that radiation may be involved not only as a tumor initiator but also as a tumor promoter, and a tumor progression-enhancing agent.