Induction of thymic lymphosarcomas in C57BL/6 mice after inoculation of weakly oncogenic viruses associated with a sub-leukemogenic radiation exposure (1.75 Gy x 2).

Abstract

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.