Apoptosis during the development of radiogenic thymic lymphomas: Effects of treatments inhibiting lymphoma development

Introduction: Whole body fractionated irradiation induces thymic lymphomas in C57BL/Ka mice after a latent period during which preleukemic cells progr essively transform into leukemic cells within an abnormal thymic microenvir onment. A bone marrow graft or repeated cytokine injections prevent lymphom a development. We think that these treatments restore altered mechanisms co ntrolling apoptosis. Materials and Methods: Apoptosis was analyzed by flow cytometry in thymocytes from different groups of mice (control, preleukemic , prevented mice). Results: The apoptotic rates did not change in freshly i solated thymocytes from different experimental groups. However, after cultu re, the level of apoptosis increased in preleukemic. thymuses; and returned to normal value in cultured thymocytes from irradiated mice after lymphoma preventing treatments. Furthermore, thymic microenvironmental factors can control thymocyte apoptosis. Conclusion: We propose that after leukemogenic irradiation there is an increase of cells with an activated suicide progra m, but that alterations of thymic environmental factors rescue them from ap optosis, allowing their further neoplastic transformation.