STUDIES ON THE ACTIVATION OF ONCOGENES IN VIRUSES AND HUMAN TUMORS

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We had previously identified ovc, a human transforming sequence activated during DNA transfection and derived from the human ovarian carcinoma cell line, OVCAR3. A portion of these sequences map to chromosome 9 and is expressed in a subset of transformed cell lines tested. We have analyzed the DNA obtained from 30 clinical samples of various types of ovarian and female reproductive tract tumors, and have detected a 10- to 15-fold amplification of these sequences in one metastatic, poorly differentiated adenocarcinoma. We have further analyzed the mechanism of restriction of growth of RD114 virus in feline fibroblasts. Although expression of reporter genes of the RD114 LTR is not restricted, expression of intact RD114 viral RNA appears to be reduced whether the genome is introduced by infection or transfection. This suggests viral components, in addition to the LTR, are involved in cellular restriction of RD114 at the transcriptional level. We have analyzed the toxic and cytostatic effects of high multiplicity infection of Mo-MuSV containing the mos oncogene. Different strains of mos-containing viruses appear to block cell proliferation in fibroblasts, and helper-free stocks of the ml strain induce both toxicity and growth inhibition. Toxicity is accompanied by the induction of abnormalities in nuclear and chromosomal structure.