Retroviruses in radiation-induced lymphomas

The nucleotide sequence of RadLV/VL₃ (T+L+), the thymotropic and leukemogenic entity of the in-vitro propagated radiation leukemia virus complex (RadLV/VL₃), is that of a recombinant retrovirus. The gag, pol and most of the env gene are very similar to the homologous regions of Akv MuLV. The 3′ end of the env gene and the LTR appear to have derived from a xenotropic MuLV. However, the LTR has acquired a feature shared by other lymphomagenic MuLVs. This feature consists in sequence rearrangements resulting in the generation of presumed enhancer elements. RadLV/VL₃(T+L+)-specific proviral sequences were found adjacent to the c-myc gene in several virus-induced thymic lymphomas of the rat, suggesting that the enhancer elements might play a role in lymphomagenesis. However, we found that the presence of a provirus at a specific DNA site can lead to an in-vitro growth advantage and to clonal cell selection independently of a lymphomagenic process. We conclude from this observation that clonal appearance of an integrated provirus in cultured radiogenic lymphoma cells does not necessarily reflect a viral induction of a radiation-induced leukemogenesis.