Generation of oncogenic mouse type C viruses: in vitro selection of carcinoma-inducing variants.

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Abstract
Type C retroviruses are endogenous in most vertebrate species. These viruses generally are of low pathogenicity in their natural hosts. Variants that contain cell-derived transforming genes were isolated infrequently in the past upon continued passage in vivo. A procedure that allows the isolation of new mouse leukemia-, sarcoma- and carcinoma-inducing type C viruses entirely in cell culture is discribed. The viruses generated after passage in chemically transformed mouse cells and selection in epithelial mink lung cells produced pulmonary adenomas and adenocarcinomas and also ovarian carcinomas. Viruses with cell-transforming capacity, as determined by their ability to induce normal murine or mink cells to form progressively growing colonies in soft agar, appeared only transiently (2-4 days) after acute infection of spontaneously or chemically transformed mouse cells by nontransforming helper viruses. These transiently appearing transforming viruses can be captured by selecting the cells that respond to their newly acquired growth-stimulating ability. This system may lend itself to the systematic isolation of tissue-specific transforming functions from any cell that can be efficiently infected by retroviruses.