Biological and morphological characteristics of phenotypic revertants appearing in interferon-treated mouse cells transformed by a human oncogene.

Phenotypic revertants appearing in interferon-treated mouse cells that had been transformed by an activated human c-Ha-ras1 oncogene (cell line RS485) were tested for several biological properties. The cloned revertants regained the growth characteristics of the untransformed parental NIH 3T3 cell line; unlike RS485 cells the revertants failed to form colonies in soft agar or to form rapidly growing tumors in nude mice. Animals inoculated with RS485 cells developed tumors within one week. In contrast, revertant clonal line 4C3 failed to form tumors four months after transplantation. Revertant 4C8 cells were tumorigenic; however, the developing tumors had increased latency, slower growth rate, and remained smaller than tumors of RS485 cells. Histopathological analysis revealed that revertant-associated fibrosarcomas were less anaplastic, less cellular and had relatively infrequent mitotic figures as compared to fibrosarcomas of RS485 cells. The result suggest the IFN-induced revertants exhibit a significantly less malignant phenotype than their parental transformed cells and that the biological differences are maintained after IFN treatment is discontinued.