Expression of the retroviral vector Neor myeloproliferative sarcoma virus (MPSV), which contains the v-mos oncogene and the neomycin resistance gene, leads to neoplastic transformation of mouse fibroblasts. Murine recombinant gamma interferon (IFN--y) could revert the neoplastic properties of established Neor MPSVtransformed cell lines to an apparently untransformed phenotype. In the presence of IFN-y, the Neor MPSV transformants showed a greater than 97% reduction of cloning efficiency in soft

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... agar, strongly reduced proliferative capacity, and morphological changes. The IFN-y-induced phenotypic reversion was preceded by a rapid and selective reduction of all retroviral RNA species, apparently due to IFN--y action on the long terminal repeat of Neor MPSV. The mRNA levels of cellular genes either remained unaffected (,I-actin) or were even enhanced (H-2) in IFN-y-treated Neor MPSV-transformed cells. Upon removal of IFN-y, retroviral gene expression was fully recovered and a gradual reappearance of the transformed phenotype of these cells within 3 weeks was noted. These data show that IFN-'y can cause a virtually complete, but reversible, inhibition of v-mos-induced neoplastic properties in transformed fibroblasts by selective down regulation of retroviral RNA levels.