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. 1990 Feb;87(3):1174–1177. doi: 10.1073/pnas.87.3.1174

Neoplastic transformation of immortalized human epidermal keratinocytes by ionizing radiation.

P Thraves 1, Z Salehi 1, A Dritschilo 1, J S Rhim 1
PMCID: PMC53433  PMID: 2405395

Abstract

Efforts to investigate the progression of events that cause human cells to become neoplastic in response to ionizing radiation have been aided by the development of tissue culture systems of epithelial cells. In the present study, nontumorigenic human epidermal keratinocytes immortalized by adenovirus type 12 and simian virus 40 have been transformed by exposure to x-ray irradiation. Such transformants showed morphological alterations, formed colonies in soft agar, and induced carcinomas when transplanted into nude mice, whereas primary human epidermal keratinocytes exposed to radiation in this manner failed to show any evidence of transformation. These findings demonstrate the malignant transformation of human primary epithelial cells in culture by the combined action of a DNA tumor virus and radiation, indicating a multistep process for radiation-induced neoplastic conversion. This in vitro system may be useful as a tool for dissecting the process of radiation-induced neoplastic transformation of human epithelial cells and for detecting previously unreported human oncogenes.

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Selected References

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

  1. Aaronson S. A., Todaro G. J. Transformation and virus growth by murine sarcoma viruses in human cells. Nature. 1970 Jan 31;225(5231):458–459. doi: 10.1038/225458a0. [DOI] [PubMed] [Google Scholar]
  2. Borek C., Ong A., Mason H. Distinctive transforming genes in x-ray-transformed mammalian cells. Proc Natl Acad Sci U S A. 1987 Feb;84(3):794–798. doi: 10.1073/pnas.84.3.794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Borek C. X-ray induced in vitro neoplastic transformation of human diploid cells. Nature. 1980 Feb 21;283(5749):776–778. doi: 10.1038/283776a0. [DOI] [PubMed] [Google Scholar]
  4. Farber E. The multistep nature of cancer development. Cancer Res. 1984 Oct;44(10):4217–4223. [PubMed] [Google Scholar]
  5. Furth M. E., Davis L. J., Fleurdelys B., Scolnick E. M. Monoclonal antibodies to the p21 products of the transforming gene of Harvey murine sarcoma virus and of the cellular ras gene family. J Virol. 1982 Jul;43(1):294–304. doi: 10.1128/jvi.43.1.294-304.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. GIRARDI A. J., JENSEN F. C., KOPROWSKI H. SV40-INDUCED TRANFORMATION OF HUMAN DIPLOID CELLS: CRISIS AND RECOVERY. J Cell Physiol. 1965 Feb;65:69–83. doi: 10.1002/jcp.1030650110. [DOI] [PubMed] [Google Scholar]
  7. Guerrero I., Calzada P., Mayer A., Pellicer A. A molecular approach to leukemogenesis: mouse lymphomas contain an activated c-ras oncogene. Proc Natl Acad Sci U S A. 1984 Jan;81(1):202–205. doi: 10.1073/pnas.81.1.202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Guerrero I., Villasante A., Corces V., Pellicer A. Activation of a c-K-ras oncogene by somatic mutation in mouse lymphomas induced by gamma radiation. Science. 1984 Sep 14;225(4667):1159–1162. doi: 10.1126/science.6474169. [DOI] [PubMed] [Google Scholar]
  9. Houweling A., van den Elsen P. J., van der Eb A. J. Partial transformation of primary rat cells by the leftmost 4.5% fragment of adenovirus 5 DNA. Virology. 1980 Sep;105(2):537–550. doi: 10.1016/0042-6822(80)90054-9. [DOI] [PubMed] [Google Scholar]
  10. Klein G., Klein E. Evolution of tumours and the impact of molecular oncology. Nature. 1985 May 16;315(6016):190–195. doi: 10.1038/315190a0. [DOI] [PubMed] [Google Scholar]
  11. Land H., Parada L. F., Weinberg R. A. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 1983 Aug 18;304(5927):596–602. doi: 10.1038/304596a0. [DOI] [PubMed] [Google Scholar]
  12. Milo G. E., Jr, DiPaolo J. A. Neoplastic transformation of human diploid cells in vitro after chemical carcinogen treatment. Nature. 1978 Sep 14;275(5676):130–132. doi: 10.1038/275130a0. [DOI] [PubMed] [Google Scholar]
  13. Namba M., Nishitani K., Fukushima F., Kimoto T., Nose K. Multistep process of neoplastic transformation of normal human fibroblasts by 60Co gamma rays and Harvey sarcoma viruses. Int J Cancer. 1986 Mar 15;37(3):419–423. doi: 10.1002/ijc.2910370314. [DOI] [PubMed] [Google Scholar]
  14. Namba M., Nishitani K., Hyodoh F., Fukushima F., Kimoto T. Neoplastic transformation of human diploid fibroblasts (KMST-6) by treatment with 60Co gamma rays. Int J Cancer. 1985 Feb 15;35(2):275–280. doi: 10.1002/ijc.2910350221. [DOI] [PubMed] [Google Scholar]
  15. Rhim J. S., Fujita J., Arnstein P., Aaronson S. A. Neoplastic conversion of human keratinocytes by adenovirus 12-SV40 virus and chemical carcinogens. Science. 1986 Apr 18;232(4748):385–388. doi: 10.1126/science.2421406. [DOI] [PubMed] [Google Scholar]
  16. Rhim J. S., Huebner R. J., Arnstein P., Kopelovich L. Chemical transformation of cultured human skin fibroblasts derived from individuals with hereditary adenomatosis of the colon and rectum. Int J Cancer. 1980 Nov 15;26(5):565–569. doi: 10.1002/ijc.2910260507. [DOI] [PubMed] [Google Scholar]
  17. Rhim J. S., Jay G., Arnstein P., Price F. M., Sanford K. K., Aaronson S. A. Neoplastic transformation of human epidermal keratinocytes by AD12-SV40 and Kirsten sarcoma viruses. Science. 1985 Mar 8;227(4691):1250–1252. doi: 10.1126/science.2579430. [DOI] [PubMed] [Google Scholar]
  18. Ruley H. E. Adenovirus early region 1A enables viral and cellular transforming genes to transform primary cells in culture. Nature. 1983 Aug 18;304(5927):602–606. doi: 10.1038/304602a0. [DOI] [PubMed] [Google Scholar]
  19. Sawey M. J., Hood A. T., Burns F. J., Garte S. J. Activation of c-myc and c-K-ras oncogenes in primary rat tumors induced by ionizing radiation. Mol Cell Biol. 1987 Feb;7(2):932–935. doi: 10.1128/mcb.7.2.932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Treisman R., Novak U., Favaloro J., Kamen R. Transformation of rat cells by an altered polyoma virus genome expressing only the middle-T protein. Nature. 1981 Aug 13;292(5824):595–600. doi: 10.1038/292595a0. [DOI] [PubMed] [Google Scholar]
  21. Weinberg R. A. Oncogenes of spontaneous and chemically induced tumors. Adv Cancer Res. 1982;36:149–163. doi: 10.1016/s0065-230x(08)60424-8. [DOI] [PubMed] [Google Scholar]
  22. van der Eb A. J., van Ormondt H., Schrier P. I., Lupker J. H., Jochemsen H., van den Elsen P. J., DeLeys R. J., Maat J., van Beveren C. P., Dijkema R. Structure and function of the transforming genes of human adenoviruses and SV40. Cold Spring Harb Symp Quant Biol. 1980;44(Pt 1):383–399. doi: 10.1101/sqb.1980.044.01.043. [DOI] [PubMed] [Google Scholar]

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