A new leukemogenic retrovirus isolated from tumor cells derived from a radio-induced lymphoma of C57BL/6 mice: analysis of the env and LTR sequences.

We report the cloning and characterization of a new ecotropic provirus encountered in a radio-induced thymic lymphoma of the C57BL/6 mouse. The provirus with an abnormally long LTR was inserted in the chromosomal DNA within the Pvt-1/MLVi-1/Mis-1 region which is a common integration site for MCF virus in mice and for Mo-MuLV in rats. This new ecotropic provirus was molecularly cloned and found to be infectious and competent for replication after transfection of murine cells.

Identification of malignant cell clones in radio-induced murine thymic lymphomas by viral and cellular probes.

The role of B ecotropic recombinant retroviruses in the emergence and the progression of radio-induced thymic lymphomas was evaluated by analyzing the cell populations present in nine primary and in in vivo propagated tumors. For this, tumor DNAs were analyzed by the Southern method using probes specific for newly acquired proviral sequences, T-cell receptor beta-chain, and immunoglobulin heavy chain genes. Our results show that primary radio-induced tumors are composed of several tumoral cell clones but do not support that malignant cell transformation and proliferation are conferred, solely, by the newly acquired ecotropic recombinant retroviral sequences.

Evidence of recombinant ecotropic provirus integration in thymic lymphomas induced by direct or indirect radiation effects.

Several investigators described the occurrence of ecotropic recombinant proviruses in the DNA of in-vivo or in-vitro propagated radio-induced lymphomas, but such proviruses were never detected in primary tumors. To assess their biological significance in the tumorigenic process, we reinvestigated the presence of new proviruses chiefly in primary radio-induced tumors and in models of radioleukemogenesis which could give additional support for their role. Such models included thymic lymphomas originating after (i) graft of non-irradiated thymuses in thymectomized irradiated mice and (ii) the injection of a B-ecotropic retrovirus (T1223/B) in association with a subleukemogenic dose of irradiation.