We have investigated the transposition of endogenous proviral genes in hematopoietic neoplasms of RFM/Un mice. Our results indicate that somtically acquired provirus is integrated at novel sites in lymphosarcomas of 5-azacytidine treated mice. Analysis of these neoplasmas and spontaneous reticulum cell sarcomas with myc, myb and mos oncogene probes has not revealed any genomic rearrangements of these genes. We have molecularly cloned three proviruses from a single RFM/Un spleen DNA sample in order to identify genes at the integration site that may be involved in the neoplastic phenotype. Analysis reveals that one clone is a complete infectious provirus, another is apparently intact but lacks infectivity, and a third has a deletion in the env gene. Restriction enzyme maps have been determined for the viral and cellular flanking regions of these clones. In collaboration with Dr. Miles Cloyd, Duke University, novel retroviruses have been isolated from RFM/Un mice. These apparent recombinant genome viruses may be important components of the etiology of RFM/Un lymphomagenesis. In collaboration with Dr. Wen Yang, Oak Ridge Natioal Laboratory, we have analyzed the structure of endogenous nonecotropic proviral genomes molecularly cloned from this strain. The LTR, prime binding site and env region of the endogenous nonecotropic proviruses are distinct from the inducible ecotropic provirus. The contribution of these endogenous elements to lymphomagensis in the RFM/Un mouse is being further studied by molecular and biologicl techniques.
