DNA amplification and neoplastic transformation mediated by a herpes simplex DNA fragment containing cell-related sequences

R. J. Jariwalla, B. Tanczos, C. Jones, J. Ortiz, S. Salimi-Lopez

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

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 BamHI 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.

Original languageEnglish (US)
Pages (from-to)1738-1742
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume83
Issue number6
DOIs
StatePublished - 1986

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