Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1970 Mar 31;131(4):863–879. doi: 10.1084/jem.131.4.863

GROWTH CHARACTERISTICS OF VIRUS-TRANSFORMED CELLS

MAXIMUM POPULATION DENSITY, INHIBITION BY NORMAL CELLS, SERUM REQUIREMENT, GROWTH IN SOFT AGAR, AND XENOGENEIC TRANSPLANTABILITY

H Eagle 1, G E Foley 1, H Koprowski 1, H Lazarus 1, E M Levine 1, R A Adams 1
PMCID: PMC2138771  PMID: 4317881

Abstract

Virus transformants (like cancer cells, cells transformed by X-ray or carcinogens, or those which have transformed spontaneously) exhibit a number of phenotypic changes which are usually associated, and which may be lost concurrently. That association is, however, not invariable. More particularly, the altered characteristics here studied (escape from contact inhibition of growth and susceptibility to inhibition by other cells, decreased serum requirement, and ability to grow in soft agar) do not, in and of themselves, endow the cell with the capacity to produce a tumor, at least as judged by the methods of assay here used. Although the question as to whether the tumorigenicity of virus transformants is causally linked to any of these associated changes cannot be answered definitively, the evidence suggests a close linkage, rather than identity, between the determinants of oncogenicity and the other properties here studied.

Full Text

The Full Text of this article is available as a PDF (866.1 KB).

Selected References

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

  1. Adams R. A., Flowers A., Davis B. J. Direct implantation and serial transplantation of human acute lymphoblastic leukemia in hamsters, SB-2. Cancer Res. 1968 Jun;28(6):1121–1125. [PubMed] [Google Scholar]
  2. Adams R. A., Foley G. E., Uzman B. G., Farber S., Lazarus S., Kleinman L. Leukemia: serial transplantation of human leukemic lymphoblasts in the newborn Syrian hamster. Cancer Res. 1967 Apr;27(4):772–783. [PubMed] [Google Scholar]
  3. Borek C., Sachs L. In vitro cell transformation by x-irradiation. Nature. 1966 Apr 16;210(5033):276–278. doi: 10.1038/210276a0. [DOI] [PubMed] [Google Scholar]
  4. Borek C., Sachs L. The difference in contact inhibition of cell replication between normal cells and cells transformed by different carcinogens. Proc Natl Acad Sci U S A. 1966 Dec;56(6):1705–1711. doi: 10.1073/pnas.56.6.1705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. EAGLE H. Amino acid metabolism in mammalian cell cultures. Science. 1959 Aug 21;130(3373):432–437. doi: 10.1126/science.130.3373.432. [DOI] [PubMed] [Google Scholar]
  6. EAGLE H. Nutrition needs of mammalian cells in tissue culture. Science. 1955 Sep 16;122(3168):501–514. doi: 10.1126/science.122.3168.501. [DOI] [PubMed] [Google Scholar]
  7. EAGLE H. Relative growth-promoting activity in tissue culture of co-factors and the parent vitamins. Proc Soc Exp Biol Med. 1956 Mar;91(3):358–361. doi: 10.3181/00379727-91-22262. [DOI] [PubMed] [Google Scholar]
  8. Eagle H., Levine E. M. Growth regulatory effects of cellular interaction. Nature. 1967 Mar 18;213(5081):1102–1106. doi: 10.1038/2131102a0. [DOI] [PubMed] [Google Scholar]
  9. Eagle H., Levine E. M., Koprowski H. Species specificity in growth regulatory effects of cellular interaction. Nature. 1968 Oct 19;220(5164):266–269. doi: 10.1038/220266a0. [DOI] [PubMed] [Google Scholar]
  10. FOLEY G. E., HANDLER A. H., ADAMS R. A., CRAIG J. M. Assessment of potential malignancy of cultured cells: further observations on the differentiation of "normal" and "neoplastic" cells maintained in vitro by hetero-transplantation in Syrian hamsters. Natl Cancer Inst Monogr. 1962 Apr;7:173–204. [PubMed] [Google Scholar]
  11. Fedoroff S. Proposed usage of animal tissue culture terms. Exp Cell Res. 1967 Jun;46(3):642–648. doi: 10.1016/0014-4827(67)90400-4. [DOI] [PubMed] [Google Scholar]
  12. Foley G. E., Handler A. H., Lynch P. M., Wolman S. R., Stulberg C. S., Eagle H. Loss of neoplastic properties in vitro. II. Observations on KB sublines. Cancer Res. 1965 Sep;25(8):1254–1261. [PubMed] [Google Scholar]
  13. HANDLER A. H., DAVIS S., SOMMERS S. C. Heterotransplantation experiments with human cancers. Cancer Res. 1956 Jan;16(1):32–36. [PubMed] [Google Scholar]
  14. Hakomori S. I., Murakami W. T. Glycolipids of hamster fibroblasts and derived malignant-transformed cell lines. Proc Natl Acad Sci U S A. 1968 Jan;59(1):254–261. doi: 10.1073/pnas.59.1.254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Holley R. W., Kiernan J. A. "Contact inhibition" of cell division in 3T3 cells. Proc Natl Acad Sci U S A. 1968 May;60(1):300–304. doi: 10.1073/pnas.60.1.300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. MONTAGNIER L., MACPHERSON I. CROISSANCE S'ELECTIVE EN G'ELOSE DE CELLULES DE HAMSTER TRANSFORM'EES PAR LE VIRUS DU POLYOME. C R Hebd Seances Acad Sci. 1964 Apr 20;258:4171–4173. [PubMed] [Google Scholar]
  18. Macintyre E., Pontén J. Interaction between normal and transformed bovine fibroblasts in culture. I. Cells transformed by Rous sarcoma virus. J Cell Sci. 1967 Sep;2(3):309–322. doi: 10.1242/jcs.2.3.309. [DOI] [PubMed] [Google Scholar]
  19. McAllister R. M., Reed G. Colonial growth in agar of cells derived from neoplastic and non-neoplastic tissues of children. Pediatr Res. 1968 Sep;2(5):356–360. doi: 10.1203/00006450-196809000-00004. [DOI] [PubMed] [Google Scholar]
  20. Pollack R. E., Green H., Todaro G. J. Growth control in cultured cells: selection of sublines with increased sensitivity to contact inhibition and decreased tumor-producing ability. Proc Natl Acad Sci U S A. 1968 May;60(1):126–133. doi: 10.1073/pnas.60.1.126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pontén J., Macintyre E. H. Interaction between normal and transformed bovine fibroblasts in culture. II. Cells transformed by polyoma virus. J Cell Sci. 1968 Dec;3(4):603–613. doi: 10.1242/jcs.3.4.603. [DOI] [PubMed] [Google Scholar]
  22. Rabinowitz Z., Sachs L. Reversion of properties in cells transformed by polyoma virus. Nature. 1968 Dec 21;220(5173):1203–1206. doi: 10.1038/2201203a0. [DOI] [PubMed] [Google Scholar]
  23. Rabinowitz Z., Sachs L. The formation of variants with a reversion of properties of transformed cells. I. Variants from polyoma-transformed cells grown in vivo. Virology. 1969 Jun;38(2):336–342. doi: 10.1016/0042-6822(69)90375-4. [DOI] [PubMed] [Google Scholar]
  24. Rabson A. S., Kirschstein R. L., Legallais F. Y. Autologous implantation of rhesus monkey cells "transformed" in vitro by simian virus 40. J Natl Cancer Inst. 1965 Dec;35(6):981–991. [PubMed] [Google Scholar]
  25. STOKER M., MACPHERSON I. SYRIAN HAMSTER FIBROBLAST CELL LINE BHK21 AND ITS DERIVATIVES. Nature. 1964 Sep 26;203:1355–1357. doi: 10.1038/2031355a0. [DOI] [PubMed] [Google Scholar]
  26. Shapiro A. L., Siegel I. M., Scharff M. D., Robbins E. Characteristics of cultured lens epithelium. Invest Ophthalmol. 1969 Aug;8(4):393–400. [PubMed] [Google Scholar]
  27. Shipman C., Jr, Vander Weide G. C., Ma B. I. Prevalence of type R virus-like particles in clones of BHK-21 cells. Virology. 1969 Aug;38(4):707–710. doi: 10.1016/0042-6822(69)90192-5. [DOI] [PubMed] [Google Scholar]
  28. Stoker M. G., Shearer M., O'Neill C. Growth inhibition of polyoma-transformed cells by contact with static normal fibroblasts. J Cell Sci. 1966 Sep;1(3):297–310. doi: 10.1242/jcs.1.3.297. [DOI] [PubMed] [Google Scholar]
  29. Temin H. M. Studies on carcinogenesis by avian sarcoma viruses. 3. The differential effect of serum and polyanions on multiplication of uninfected and converted cells. J Natl Cancer Inst. 1966 Aug;37(2):167–175. [PubMed] [Google Scholar]
  30. Todaro G. J., Green H. Cell growth and the initiation of transformation by SV40. Proc Natl Acad Sci U S A. 1966 Feb;55(2):302–308. doi: 10.1073/pnas.55.2.302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Yerganian G., Nell M. A., Cho S. S., Hayford A. H., Ho T. Virus-associated gain and loss of proliferative and neoplastic properties of normal and virus-transformed diploid cell lines. Natl Cancer Inst Monogr. 1968 Dec;29:241–268. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES