V-ONC MUTATION ASSOCIATED WITH HOST-CELL GROWTH IN RETROVIRAL TUMORS

In sarcomagenesis in rats infected neonatally with feline sarcoma viru s (ST-FeSV), v-fes product (P85) was previously shown by us to be a pr edictive anti preventive determinant. In order to explore the part pla yed by P85 in tumor suppression, DNA was extracted from precancerous g ranulomas and from slow or rapid growing sarcomas Induced by neonatal injection of the virus. The v-fes signal from extracted DNA was analyz ed by PCR-SSCP. The prototype v-fes gene signal was detected in most l esions and found to be generally amplified in rapid growing sarcomas a nd in some granulomas. Several v-fes homologs showing varying mobiliti es in gel were seen in most sarcomas and some granulomas with or witho ut the prototype v-fes signal. In slow growing sarcomas and granulomas induced in hosts that were immunized with ST-FeSV induced syngeneic s arcoma and proved to carry IgG antibody to P85, the prototype v-fes ge ne was found to be down-regulated and v-fes homologs were found to be reduced in number or eliminated. These results suggest that the develo pment of v-fes mutations is associated with the growth potential of ce lls carrying the v-fes gene, and that host immunity to v-onc product i nfluences the development of virogene rearrangements and results in sl ow and suppressed growth of tumors caused by neonatal infection with r etrovirus.