Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1980 Nov;42(5):756–764. doi: 10.1038/bjc.1980.309

Effect of 12-O-tetradecanoylphorbol-13-acetate on two charateristics of transformation acquired sequentially by ENU-exposed rat brain cells.

J P Roscoe, T A Hince, P J Claisse, D P Winslow
PMCID: PMC2010565  PMID: 7193044

Abstract

Cultures derived from rat brains at different times during the latent period of brain-tumour induction by N-ethyl-N-nitrosourea (ENU) showed increased plasminogen activator (PA) activity before being able to form colonies in agar. Control cultures from buffer-exposed animals showed neither property at comparable passages. More detailed investigations, using a culture derived from foetal brains only 2 days after exposure to ENU and clones from this culture, showed a sequence of low PA activity, then increased activity, followed by the ability to form colonies in agar, suggesting progressive transformation of cells in culture. Continuous culturing in the presence of the mouse skin tumour promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), did not accelerate the rate at which these two properties were acquired, but did cause a much greater increase of PA activity once this started to rise. If included in the assay mixture TPA also increased the PA activity of the cells. It therefore appears that in this system TPA can modulate PA activity under certain circumstances.

Full text

PDF
756

Selected References

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

  1. Barrett J. C., Crawford B. D., Grady D. L., Hester L. D., Jones P. A., Benedict W. F., Ts'o P. O. Temporal acquistion of enhanced fibrinolytic activity by syrian hamster embryo cells following treatment with benzo(a)pyrene. Cancer Res. 1977 Oct;37(10):3815–3823. [PubMed] [Google Scholar]
  2. Barrett J. C., Crawford B. D., Mixter L. O., Schechtman L. M., Ts'o P. O., Pollack R. Correlation of in vitro growth properties and tumorigenicity of Syrian hamster cell lines. Cancer Res. 1979 May;39(5):1504–1510. [PubMed] [Google Scholar]
  3. Barrett J. C., Ts'o P. O. Evidence for the progressive nature of neoplastic transformation in vitro. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3761–3765. doi: 10.1073/pnas.75.8.3761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Borland R., Hard G. C. Early appearance of "transformed" cells from the kidneys of rats treated with a "single" carcinogenic dose of dimethylnitrosamine (DMN) detected by culture in vitro. Eur J Cancer. 1974 Mar;10(3):177–184. doi: 10.1016/0014-2964(74)90151-0. [DOI] [PubMed] [Google Scholar]
  5. Druckrey H., Ivanković S., Preussmann R. Teratogenic and carcinogenic effects in the offspring after single injection of ethylnitrosourea to pregnant rats. Nature. 1966 Jun 25;210(5043):1378–1379. doi: 10.1038/2101378a0. [DOI] [PubMed] [Google Scholar]
  6. Hince T. A., Roscoe J. P. Differences in pattern and level of plasminogen activator production between a cloned cell line from an ethylnitrosourea-induced glioma and one from normal adult rat brain. J Cell Physiol. 1980 Aug;104(2):199–207. doi: 10.1002/jcp.1041040209. [DOI] [PubMed] [Google Scholar]
  7. Hince T. A., Roscoe J. P. Fibrinolytic activity of cultured cells derived during ethylnitrosourea-induced carcinogenesis of rat brain. Br J Cancer. 1978 Mar;37(3):424–433. doi: 10.1038/bjc.1978.63. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Jones P. A., Laug W. E., Gardner A., Nye C. A., Fink L. M., Benedict W. F. In vitro correlates of transformation in C3H/10T1/2 clone 8 mouse cells. Cancer Res. 1976 Aug;36(8):2863–2867. [PubMed] [Google Scholar]
  9. Jones P., Benedict W., Strickland S., Reich E. Fibrin overlay methods for the detection of single transformed cells and colonies of transformed cells. Cell. 1975 Jul;5(3):323–329. doi: 10.1016/0092-8674(75)90108-7. [DOI] [PubMed] [Google Scholar]
  10. Laerum O. D., Rajewsky M. F. Neoplastic transformation of fetal rat brain cells in culture after exposure to ethylnitrosourea in vivo. J Natl Cancer Inst. 1975 Nov;55(5):1177–1187. doi: 10.1093/jnci/55.5.1177. [DOI] [PubMed] [Google Scholar]
  11. Lasne C., Gentil A., Chouroulinkov I. Two-stage malignant transformation of rat fibroblasts in tissue culture. Nature. 1974 Feb 15;247(5441):490–491. doi: 10.1038/247490a0. [DOI] [PubMed] [Google Scholar]
  12. Lee L. S., Weinstein I. B. Tumor-promoting phorbol esters inhibit binding of epidermal growth factor to cellular receptors. Science. 1978 Oct 20;202(4365):313–315. doi: 10.1126/science.308698. [DOI] [PubMed] [Google Scholar]
  13. MACPHERSON I., MONTAGNIER L. AGAR SUSPENSION CULTURE FOR THE SELECTIVE ASSAY OF CELLS TRANSFORMED BY POLYOMA VIRUS. Virology. 1964 Jun;23:291–294. doi: 10.1016/0042-6822(64)90301-0. [DOI] [PubMed] [Google Scholar]
  14. Mondal S., Brankow D. W., Heidelberger C. Two-stage chemical oncogenesis in cultures of C3H/10T1/2 cells. Cancer Res. 1976 Jul;36(7 Pt 1):2254–2260. [PubMed] [Google Scholar]
  15. Ossowski L., Unkeless J. C., Tobia A., Quigley J. P., Rifkin D. B., Reich E. An enzymatic function associated with transformation of fibroblasts by oncogenic viruses. II. Mammalian fibroblast cultures transformed by DNA and RNA tumor viruses. J Exp Med. 1973 Jan 1;137(1):112–126. doi: 10.1084/jem.137.1.112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Poiley J. A., Raineri R., Pienta R. J. Two-stage malignant transformation in hamster embryo cells. Br J Cancer. 1979 Jan;39(1):8–14. doi: 10.1038/bjc.1979.2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Roscoe J. P., Claisse P. J. A sequential in vivo-in vitro study of carcinogenesis induced in the rat brain by ethylnitrosourea. Nature. 1976 Jul 22;262(5566):314–316. doi: 10.1038/262314a0. [DOI] [PubMed] [Google Scholar]
  18. Roscoe J. P., Claisse P. J. Analysis of N-ethyl-N-nitrosourea-induced brain carcinogenesis by sequential culturing during the latent period. I. Morphology and tumorigenicity of the cultured cells and their growth in agar. J Natl Cancer Inst. 1978 Aug;61(2):381–390. [PubMed] [Google Scholar]
  19. Roscoe J. P. In-vivo-in-vitro analysis of ethylnitrosourea-induced brain carcinogenesis in the rat. Br Med Bull. 1980 Jan;36(1):33–38. doi: 10.1093/oxfordjournals.bmb.a071610. [DOI] [PubMed] [Google Scholar]
  20. Roscoe J. P., Winslow D. P. Increased ability of ethylnitrosourea-exposed brain cells to survive suspension in agar. Br J Cancer. 1980 Jun;41(6):992–995. doi: 10.1038/bjc.1980.180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Shoyab M., De Larco J. E., Todaro G. J. Biologically active phorbol esters specifically alter affinity of epidermal growth factor membrane receptors. Nature. 1979 May 31;279(5712):387–391. doi: 10.1038/279387a0. [DOI] [PubMed] [Google Scholar]
  22. Strickland S., Reich E., Sherman M. I. Plasminogen activator in early embryogenesis: enzyme production by trophoblast and parietal endoderm. Cell. 1976 Oct;9(2):231–240. doi: 10.1016/0092-8674(76)90114-8. [DOI] [PubMed] [Google Scholar]
  23. Unkeless J. C., Tobia A., Ossowski L., Quigley J. P., Rifkin D. B., Reich E. An enzymatic function associated with transformation of fibroblasts by oncogenic viruses. I. Chick embryo fibroblast cultures transformed by avian RNA tumor viruses. J Exp Med. 1973 Jan 1;137(1):85–111. doi: 10.1084/jem.137.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wigler M., Weinstein I. B. Tumour promotor induces plasminogen activator. Nature. 1976 Jan 22;259(5540):232–233. doi: 10.1038/259232a0. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES