Cellular aspects of the pathogenesis of radiation--induced thymic lymphomas in C57 BL mice (review)

Abstract

Radiation-induced thymic lymphomas in C57Bl/Ka mice are interesting models for studying the successive steps of carcinogenesis. Irradiation initiates "preleukemic" cells, which are promoted to become neoplastic. Studies in mice in which lymphoma development is inhibited by a bone marrow transplantation after irradiation suggest that radiation--induced alterations to the T cell lineage, and particularly to thymic microenvironment, are critical for the promotion of preleukemic cells. It is proposed that the lack of physiological differentiation signals within the thymus, as a result of irradiation, allows these cells to escape the normal controls of thymocyte production and pushes them towards neoplastic transformation. A disturbance in the production of cytokines may be involved, since exogenous cytokines, such as Interferon gamma or Tumor Necrosis Factor a, can inhibit radiation-induced lymphomagenesis, reproducing the effects of bone marrow transplantation. The model is thus suitable for studying the mechanisms of carcinogenesis and designing biological manipulation devoted to cancer prevention in individuals who have been exposed to oncogenic agents.