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. 1981 Apr;78(4):2616–2619. doi: 10.1073/pnas.78.4.2616

Herpes simplex virus (type 1) thymidine kinase gene does not transform cells morphologically.

B Hampar, J G Derge, A L Boyd, M A Tainsky, S D Showalter
PMCID: PMC319400  PMID: 6264486

Abstract

BALB/c-derived 10E2 cells were made thymidine kinase(TK)-negative and one isolated clone (B2) was used for studying morphological and biochemical transformations by herpes simplex virus (HSV) type 1 (strain 10412). The B2 cells displayed a "normal" flat appearance and were nontumorigenic in nude mice when tested at frequent intervals over a period of 45 subcultures. B2 cells infected with UV-irradiated HSV (UV-HSV) and maintained in normal growth medium showed foci of spindle-shaped cells after one subculture. The cells from these morphologically transformed foci were tumorigenic in nude mice and were TK negative. B2 cells infected with UV-HSV or transfected with the HSV-1 TK gene and maintained in TK-selective medium showed discrete colonies of cells which displayed a normal flat appearance and expressed the viral TK enzyme. These biochemically transformed B2 cells were nontumorigenic in nude mice. The findings with B2 cells indicate that biochemical and morphological transformations by HSV-1 are independent events and suggest that the HSV-1 TK gene is a suitable vehicle for introducing non-TK genes into cells to assess their transforming potential.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Auerbach R., Morrissey L. W., Sidky Y. A. Gradients in tumour growth. Nature. 1978 Aug 17;274(5672):697–699. doi: 10.1038/274697a0. [DOI] [PubMed] [Google Scholar]
  2. Camacho A., Spear G. Transformation of hamster embryo fibroblasts by a specific fragment of the herpes simplex virus genome. Cell. 1978 Nov;15(3):993–1002. doi: 10.1016/0092-8674(78)90283-0. [DOI] [PubMed] [Google Scholar]
  3. Colbere-Garapin F., Chousterman S., Horodniceanu F., Kourilsky P., Garapin A. C. Cloning of the active thymidine kinase gene of herpes simplex virus type 1 in Escherichia coli K-12. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3755–3759. doi: 10.1073/pnas.76.8.3755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Duff R., Rapp F. Oncogenic transformation of hamster cells after exposure to herpes simplex virus type 2. Nat New Biol. 1971 Sep 8;233(36):48–50. doi: 10.1038/newbio233048a0. [DOI] [PubMed] [Google Scholar]
  5. Enquist L. W., Madden M. J., Schiop-Stanley P., Vande Woude G. F. Cloning of herpes simplex type 1 DNA fragments in a bacteriophage lambda vector. Science. 1979 Feb 9;203(4380):541–544. doi: 10.1126/science.216076. [DOI] [PubMed] [Google Scholar]
  6. Frenkel N., Locker H., Cox B., Roizman B., Rapp F. Herpes simplex virus DNA in transformed cells: sequence complexity in five hamster cell lines and one derived hamster tumor. J Virol. 1976 Jun;18(3):885–893. doi: 10.1128/jvi.18.3.885-893.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hampar B., Boyd A. L., Derge J. G., Zweig M., Eader L., Showalter S. D. Comparison of properties of mouse cells transformed spontaneously by ultraviolet light-irradiated herpes simplex virus or by simian virus 40. Cancer Res. 1980 Jul;40(7):2213–2222. [PubMed] [Google Scholar]
  8. Jariwalla R. J., Aurelian L., Ts'o P. O. Tumorigenic transformation induced by a specific fragment of DNA from herpes simplex virus type 2. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2279–2283. doi: 10.1073/pnas.77.4.2279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kit S., Leung W. C., Trkula D., Jorgensen G. Gel electrophoresis and isoelectric focusing of mitochondrial and viral-induced thymidine kinases. Int J Cancer. 1974 Feb 15;13(2):203–218. doi: 10.1002/ijc.2910130208. [DOI] [PubMed] [Google Scholar]
  10. LITTLEFIELD J. W. SELECTION OF HYBRIDS FROM MATINGS OF FIBROBLASTS IN VITRO AND THEIR PRESUMED RECOMBINANTS. Science. 1964 Aug 14;145(3633):709–710. doi: 10.1126/science.145.3633.709. [DOI] [PubMed] [Google Scholar]
  11. Lai E. C., Woo S. L., Bordelon-Riser M. E., Fraser T. H., O'Malley B. W. Ovalbumin is synthesized in mouse cells transformed with the natural chicken ovalbumin gene. Proc Natl Acad Sci U S A. 1980 Jan;77(1):244–248. doi: 10.1073/pnas.77.1.244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Leiden J. M., Frenkel N., Rapp F. Identification of the herpes simplex virus DNA sequences present in six herpes simplex virus thymidine kinase-transformed mouse cell lines. J Virol. 1980 Jan;33(1):272–285. doi: 10.1128/jvi.33.1.272-285.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Maitland N. J., McDougall J. K. Biochemical transformation of mouse cells by fragments of herpes simplex virus DNA. Cell. 1977 May;11(1):233–241. doi: 10.1016/0092-8674(77)90334-8. [DOI] [PubMed] [Google Scholar]
  14. Mantei N., Boll W., Weissmann C. Rabbit beta-globin mRNA production in mouse L cells transformed with cloned rabbit beta-globin chromosomal DNA. Nature. 1979 Sep 6;281(5726):40–46. doi: 10.1038/281040a0. [DOI] [PubMed] [Google Scholar]
  15. Munyon W., Kraiselburd E., Davis D., Mann J. Transfer of thymidine kinase to thymidine kinaseless L cells by infection with ultraviolet-irradiated herpes simplex virus. J Virol. 1971 Jun;7(6):813–820. doi: 10.1128/jvi.7.6.813-820.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Parris D. S., Dixon R. A., Schaffer P. A. Physical mapping of herpes simplex virus type 1 ts mutants by marker rescue: correlation of the physical and genetic maps. Virology. 1980 Jan 30;100(2):275–287. doi: 10.1016/0042-6822(80)90519-x. [DOI] [PubMed] [Google Scholar]
  17. Reyes G. R., LaFemina R., Hayward S. D., Hayward G. S. Morphological transformation by DNA fragments of human herpesviruses: evidence for two distinct transforming regions in herpes simplex virus types 1 and 2 and lack of correlation with biochemical transfer of the thymidine kinase gene. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 1):629–641. doi: 10.1101/sqb.1980.044.01.066. [DOI] [PubMed] [Google Scholar]
  18. Summers W. C., Summers W. P. [125I]deoxycytidine used in a rapid, sensitive, and specific assay for herpes simplex virus type 1 thymidine kinase. J Virol. 1977 Oct;24(1):314–318. doi: 10.1128/jvi.24.1.314-318.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wigler M., Pellicer A., Silverstein S., Axel R., Urlaub G., Chasin L. DNA-mediated transfer of the adenine phosphoribosyltransferase locus into mammalian cells. Proc Natl Acad Sci U S A. 1979 Mar;76(3):1373–1376. doi: 10.1073/pnas.76.3.1373. [DOI] [PMC free article] [PubMed] [Google Scholar]

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