Thymic lymphosarcomas obtained by X-rays in association with a weakly leukemogenic virus: cellular studies

The association in C57BL/6 mice of a subleukemogenic radiation dose (1.75 Gy X 2) which induces 7% of thymic lymphosarcomas (TL) with the injection of a weakly oncogenic B-tropic retrovirus responsible for 5% of TL resulted in a higher incidence of TL (31%) than expected from a simple cumulative effect when the viral injection preceded the irradiations (VX protocol). When virus was injected after irradiation (XV protocol) TL incidence (19%) was not significantly different from that of a cumulative phenomenon. The B-tropic virus used (1223) was isolated from RadLV-Rs extract and cloned. The TL incidence correlates with the presence of virus firstly in the thymus and bone marrow (BM) during the preleukemic period, secondly in the cell lines established in vitro from TL obtained in both protocols. This suggests that B-tropic viruses derepressed by 4 radiation doses of 1.75 Gy might be similarly implicated in the mechanism of radio-induced TL. This hypothesis is further supported by the evidence that BM restoration inhibited leukemogenesis in processes induced either by 4 radiation doses of 1.75 Gy or by the association of 2 radiation doses and viral injection whereas it has no effect on TL induced by highly oncogenic thymotropic viruses. Transplantation of BM cells from animals which had been submitted shortly before to leukemogenic VX protocol failed to induce donor type TL or leukemias in irradiated recipients suggesting that preleukemic cells either are not present or cannot be detected. However a high incidence of recipient TL was observed indicating that viruses were transferred with the grafted cells.