The lack of v-src involvement in tumorigenicity of marmoset cells transformed in vitro with Rous sarcoma virus.

The transformation of nonhuman primate marmoset cells by Rous sarcoma virus of Schmidt-Ruppin strain (RSV-SR) generates transformants which lack tumorigenicity in allo- and xenogeneic hosts. Marmoset cells acquire this property when they are transformed by RSV rescued from non-tumorigenic allogeneic cells. One of the rescued RSV, when used to infect marmoset kidney cells in vitro, yielded transformants which became tumorigenic in adult allogeneic hosts. Cytogenetic and molecular analyses of transformants revealed progressive genetic changes from cell diploidy to aneuploidy and from the presence to the loss of v-src during propagation in vitro. The loss of v-src in transformed cells coincided with the evolution of aneuploid cell clone with specific marker chromosome (M1). Although both early passage diploid and late passage aneuploid transformants were tumorigenic, the induced tumors originated from different type of cells. Tumors induced by diploid- and v-src-positive transformants were derived predominantly from the host cells, while tumors induced by late-passage transformants and with deleted v-src originated from an aneuploid cell clone that contained a rearranged M1 marker chromosome. These results suggest that besides the v-src oncogene, proviral integration can facilitate chromosomal rearrangements that contribute to tumorigenic transformation of nonhuman primate cells in vitro.