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. 1985 Aug;82(15):5005–5009. doi: 10.1073/pnas.82.15.5005

A contact-insensitive subpopulation in Syrian hamster cell cultures with a greater susceptibility to chemically induced neoplastic transformation.

S Nakano, H Ueo, S A Bruce, P O Ts'o
PMCID: PMC390487  PMID: 3860840

Abstract

We previously have identified a subpopulation of contact-insensitive (CS-) cells which lacks density-dependent inhibition of cell division in primary and low-passage cultures of Syrian hamster embryonic (SHE) fibroblastic cells. Further, we have shown that the proportion of these CS- cells declines as a result of the stable phenotypic conversion of the CS- cells to contact-sensitive (CS+) cells. To determine whether these transient CS- cells are more sensitive to carcinogenic/mutagenic perturbation, the susceptibility to neoplastic transformation and somatic mutation induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was examined in clonally isolated cell cultures containing various proportions of CS- cells (0.02-4%). The frequencies of morphological transformation, focus formation, and neoplastic transformation showed a positive correlation to the proportion of CS- cells in the treated cultures. In contrast, the frequency of MNNG-induced somatic mutation at the Na+,K+-ATPase locus was similar among cultures varying in their proportion of CS- cells. Thus, there is a transient subpopulation of CS- cells in primary SHE cell cultures that is more susceptible to neoplastic transformation although equally susceptible to induced point mutation. This dissociation between somatic point mutation and neoplastic transformation indicates a fundamental difference in the nature of these two phenomena. A possible relationship between the propensity of CS- cells (versus CS+ cells) to carcinogen-induced neoplastic transformation and the state of differentiation of the CS- cells is discussed.

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Selected References

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

  1. Barrett J. C., Bias N. E., Ts'o P. O. A mammalian cellular system for the concomitant study of neoplastic transformation and somatic mutation. Mutat Res. 1978 Apr;50(1):121–136. doi: 10.1016/0027-5107(78)90067-2. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Barrett J. C., Ts'o P. O. Relationship between somatic mutation and neoplastic transformation. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3297–3301. doi: 10.1073/pnas.75.7.3297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Benedict W. F., Banerjee A., Gardner A., Jones P. A. Induction of morphological transformation in mouse C3H/10T1/2 clone 8 cells and chromosomal damage in hamster A(T1)C1-3 cells by cancer chemotherapeutic agents. Cancer Res. 1977 Jul;37(7 Pt 1):2202–2208. [PubMed] [Google Scholar]
  5. Boone C. W., Jacobs J. B. Sarcomas routinely produced from putatively nontumorigenic Balb/3T3 and C3H/10T1/2 cells by subcutaneous inoculation attached to plastic platelets. J Supramol Struct. 1976;5(2):131–137. doi: 10.1002/jss.400050204. [DOI] [PubMed] [Google Scholar]
  6. Borek C., Sachs L. Cell susceptibility to transformation by x-irradiation and fixation of the transformed state. Proc Natl Acad Sci U S A. 1967 May;57(5):1522–1527. doi: 10.1073/pnas.57.5.1522. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Casto B. C. Enhancement of adenovirus transformation by treatment of hamster cells with ultraviolet irradiation, DNA base analogs, and dibenz(a,h)anthracene. Cancer Res. 1973 Feb;33(2):402–407. [PubMed] [Google Scholar]
  8. Casto B. C., Janosko N., DiPaolo J. A. Development of a focus assay model for transformation of hamster cells in vitro by chemical carcinogens. Cancer Res. 1977 Oct;37(10):3508–3515. [PubMed] [Google Scholar]
  9. Huberman E., Sachs L. Cell susceptibility to transformation and cytotoxicity by the carcinogenic hydrocarbon benzo[a]pyrene. Proc Natl Acad Sci U S A. 1966 Oct;56(4):1123–1129. doi: 10.1073/pnas.56.4.1123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Little J. B. Relationship between DNA repair capacity and cellular aging. Gerontology. 1976;22(1-2):28–55. doi: 10.1159/000212123. [DOI] [PubMed] [Google Scholar]
  11. Mintz B., Illmensee K. Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3585–3589. doi: 10.1073/pnas.72.9.3585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Nakano S., Bruce S. A., Ueo H., Ts'o P. O. A qualitative and quantitative assay for cells lacking postconfluence inhibition of cell division: characterization of this phenotype in carcinogen-treated Syrian hamster embryo cells in culture. Cancer Res. 1982 Aug;42(8):3132–3137. [PubMed] [Google Scholar]
  13. Nakano S., Ts'o P. O. Cellular differentiation and neoplasia: characterization of subpopulations of cells that have neoplasia-related growth properties in Syrian hamster embryo cell cultures. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4995–4999. doi: 10.1073/pnas.78.8.4995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pienta R. J., Poiley J. A., Lebherz W. B., 3rd Morphological transformation of early passage golden Syrian hamster embryo cells derived from cryopreserved primary cultures as a reliable in vitro bioassay for identifying diverse carcinogens. Int J Cancer. 1977 May 15;19(5):642–655. doi: 10.1002/ijc.2910190508. [DOI] [PubMed] [Google Scholar]
  15. Pierce G. B., Lewis S. H., Miller G. J., Moritz E., Miller P. Tumorigenicity of embryonal carcinoma as an assay to study control of malignancy by the murine blastocyst. Proc Natl Acad Sci U S A. 1979 Dec;76(12):6649–6651. doi: 10.1073/pnas.76.12.6649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Stockdale F. E. DNA synthesis in differentiating skeletal muscle cells: initiation by ultraviolet light. Science. 1971 Mar 19;171(3976):1145–1147. doi: 10.1126/science.171.3976.1145. [DOI] [PubMed] [Google Scholar]
  17. Taylor S. M., Jones P. A. Multiple new phenotypes induced in 10T1/2 and 3T3 cells treated with 5-azacytidine. Cell. 1979 Aug;17(4):771–779. doi: 10.1016/0092-8674(79)90317-9. [DOI] [PubMed] [Google Scholar]
  18. Umeda M., Iype P. T. An improved expression of in vitro transformation rate based on cytotoxicity produced by chemical carcinogens. Br J Cancer. 1973 Jul;28(1):71–74. doi: 10.1038/bjc.1973.72. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Yuspa S. H., Morgan D. L. Mouse skin cells resistant to terminal differentiation associated with initiation of carcinogenesis. Nature. 1981 Sep 3;293(5827):72–74. doi: 10.1038/293072a0. [DOI] [PubMed] [Google Scholar]

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