Radiation leukemogenesis: quantitative relationship between pre-leukemic cells in the thymus and lymphoma induction

Fractionated irradiation of C57BL/6 mice induces a population of pre-leukemic (PL) cells that progress into mature thymic lymphomas after a latency of 4 to 6 months. Transfer of graded numbers of thymocytes from an irradiated mouse into recipient mice indicated that PL cells first appear in the thymus 6 weeks after irradiation. The initial proportion of the thymic PL cells is > or = 10(-5) and their frequency continuously increases with time, reaching > or = 10(-3) 10 weeks after irradiation. The PL cell population that emerges early during the pre-malignant latency consists of pleioclonal T lymphocytes. However, within 4 weeks a dominant PL clone can be detected which becomes the progenitor of a clonal lymphoma 9 to 15 weeks later. These results suggest that radiation leukemogenesis involves continuous accumulation of pleioclonal PL cells in the thymus, one of which is then selected for further maturation into frank lymphoma.