DNA amplification and neoplastic transformation mediated by a herpes simplex DNA fragment containing cell-related sequences.
The transforming potential of the herpes simplex virus type 2 (HSV-2) BamHI fragment E (map position 0.533-0.583) encoding the 140-kDa ribonucleotide reductase was assayed by transfection in established Rat-2 cells. Foci of refractile, morphologically distinguishable cells were induced at lower efficiency and after a longer incubation period as compared to the human tumor oncogene EJ-Ha-ras. Focus-derived BamHI fragment E-transformed cell lines formed medium-to-large (0.1-0.25 mm) colonies in soft agar and were tumorigenic in immunocompetent syngeneic rats. Southern blot analysis of normal rat DNA after EcoRI digestion revealed specific DNA segments homologous to HSV-2 BamHI fragment-E DNA. In BamHI fragment E-transformed and tumor-derived lines, about 8- to 30-fold amplification was detected in a subset of the specific HSV-related DNA segments. In addition, extrachromosomal DNA was isolated from transformed cells by plasmid rescue and contained the left-hand 70% of HSV-2 Bam HI fragment E fused to rat DNA. These results indicate the presence in normal cells of nonrepetitive DNA segments, related to the transforming HSV-2 fragment, that can be targeted for genetic alterations associated with neoplastic transformation.
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002470:Cell Survival; D002472:Cell Transformation, Viral; D003001:Cloning, Molecular; D004262:DNA Restriction Enzymes; D004274:DNA, Recombinant; D004279:DNA, Viral / Q000235:genetics / Q000502:physiology*; D005784:Gene Amplification; D005814:Genes, Viral; D009857:Oncogenes; D051381:Rats; D018139:Simplexvirus / Q000235:genetics / Q000502:physiology*
D004274:DNA, Recombinant; D004279:DNA, Viral; D004262:DNA Restriction Enzymes