B-ecotropic retroviruses arise frequently in old or irradiated C57BL/6 mice as a consequence of a genetic recombination between endogenous eco- and xenotropic retroviruses. They are weakly oncogenic and express a very low tropism for thymic cells. However, their activation by X-rays and the subsequent insertion of new proviral sequences in the cell genome of in vivo- and in vitro-passaged tumors suggest that they might play a role in radioleukemogenesis. To study this possibility, a cloned B-ecotropic virus (1223) was injected into C57BL/6 mice subjected to a subleukemogenenic irradiation which induces only 7% of thymic lymphosarcomas (TL). When it was injected prior to or after irradiation, 1223 induced respectively 31% and 19% of TL. The incidence of TL in the different groups closely correlated with virus expression in hematopoietic tissues during the preleukemic period. Thus, irradiation seems to amplify bone marrow (BM) and thymic cell population(s) which play a decisive role in viral expression. A recombinant provirus (presumably the injected 1223) was detected in the genomic DNA of all tumors tested irrespective of the inductive protocol. BM restoration, which does not inhibit TL produced by highly oncogenic passaged viruses, but prevents the development of TL induced by 4 doses of 1.75 Gy, also provided strong protection in the present experiments. The present data support the hypothesis whereby weakly oncogenic B-ecotropic viruses similar to those activated by radiation might be involved in the development of TL.

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The present experiments are an attempt to precise the type and localization of the cells involved in the protective effect of hemopoietic suspensions against the radiation-induced thymic lymphosarcoma (TLS) of C57BL/6 mice. Inocula containing variable numbers of BM or spleen CFUs from 60-day-old and 360-day-old donors were tested. According to their origin, the suspensions differed with respect to the CFU replication rate, the CFU ability to differentiate towards the T lineage and the content of the suspensions in thymic precursors. Two levels of inhibition were observed: BM suspensions from 60-day-old donors containing 1,500 CFUs had the best protective effect: 14.5% of TLS; 1,500 CFUs from 360-day-old donors were slightly but not significantly less efficient (28.5%). The second level of inhibition (36-46% of TLS) was obtained with all the following inocula: a) 1,200 and 300 spleen CFUs or 300 and 95 BM CFUs from 60-day-old donors, b) 1,500 spleen CFUs from aged donors. Seventy-six spleen CFUs from 60-day-old donors, 120 BM or 175 spleen CFUs from aged donors had no effect. These results suggest that in addition to the high replication rate of the BM CFUs as compared with spleen CFUs, cells endowed with an optimal protective effect are present in BM suspensions and are either absent or present in very small amount in spleen suspensions. These cells which induce an early repopulation of the thymus might correspond to thymic precursors.