STAGES IN THE DEVELOPMENT OF RADIATION-INDUCED THYMIC LYMPHOMAS IN C57 BL KA MICE - PRELEUKEMIC CELLS BECOME PROGRESSIVELY RESISTANT TO THETUMOR PREVENTING EFFECTS OF A BONE-MARROW GRAFT/

Fractionated whole body irradiation induces thymic lymphomas in C57 BL /Ka mice after 6-12 months. A graft of normal congenic bone marrow cel ls immediately after the last irradiation prevents the development of lymphomas by inducing the disappearance of preleukemic cells. When suc h a graft is performed one month later, it does not inhibit the emerge nce of tumors. It could be because, one month after irradiation, prele ukemic cells become insensitive to the effects of the grafted bone mar row on their leukemogenic potential. To check this hypothesis, we have investigated the capacity of grafted bone marrow cells to prevent the development of lymphomas in mice inoculated with radiation-induced pr eleukemic cells collected at several time intervals after the completi on of the radiation regimen. It was found that the bone marrow graft r educed the incidence of thymic lymphoma at day 2 (10 vs. 43%; p < 0.01 ) and 10 (39 vs. 86%; p < 0.01) but not at day 15 (64 vs. 80%; NS) or 30 (93 vs. 82%; NS). The inefficacy of the marrow graft was not associ ated with proliferation of the inoculate in the recipient thymus nor w ith inhibition by preleukemic cells of thymic repopulation by bone mar row precursors. The data provide evidence that preleukemic cells under go intrinsic changes which are reflected by the acquisition of resista nce to bone marrow grafts.