Induction of tumorigenesis and chromosomal abnormalities in human amniocytes infected with simian virus 40 and Kirsten sarcoma virus.
Cell cultures of epithelial-like human amniocytes were infected with simian virus 40 (SV40) and Kirsten sarcoma virus (KSV) in various sequential orders, and tested for agar growth, chromosome abnormalities, and tumorigenesis in the nude mouse assay. We observed that regardless of the order in which the viruses were introduced, the doubly infected cells always exhibited the typical SV40 premalignantly transformed phenotype before changing to the malignant phenotype. All doubly transformed cells from different cell donors produced tumors in adult and suckling nude athymic mice, classified as poorly differentiated sarcomas. Infection with SV40 alone conferred extended life span and accelerated growth without the malignant capability of tumor production. Kirsten sarcoma virus alone produced only focal cell alterations with no change in cell longevity or tumorigenesis. Chromosome studies of the premalignant and malignant cells from one cell donor did not reveal any significant clonal development for marker chromosomes in either cell line. Chromosome 12, which carries the homologous cellular oncogene to KSV, had no increase in aberrations in the malignant cells. Chromosome 8 was most often involved in aberrations, and the most frequent aberration for both series was dicentric chromosomes due to telomere fusion. For other translocations the breakpoints were almost exclusively in the centromere regions. The vulnerability of telomere and centromere regions to the free virus present in these precrisis cells is discussed, and similarities in regard to types of aberrations in transfection experiments are noted.
D000650:Amnion / Q000166:cytology / Q000382:microbiology; D000818:Animals; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000235:genetics*; D025063:Chromosome Disorders; D006801:Humans; D007621:Karyotyping; D007708:Kirsten murine sarcoma virus / Q000472:pathogenicity*; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000382:microbiology*; D011003:Ploidies; D009053:Sarcoma Viruses, Murine / Q000472:pathogenicity*; D013539:Simian virus 40 / Q000472:pathogenicity*