Summary
Transfection of primary cultures of human cells with origin of replication deficient SV40 DNA has been carried out by others to generate in vitro models of malignant transformation in vivo. The present work describes progressive alterations in karyotype and phenotype in one such transfected (neuroglial) cell line (SVG). After repeated passage, recognisable marker chromosomes evolved. These may be related to karyotypic anomalies found in human glial tumors. Accompanying the evolution in karyotype were changes in phenotype. Although presaging malignant transformation, these stopped short of actual tumorigenicity.
Similar content being viewed by others
References
Freshney RI: Culture of animal cells: a manual of basic technique. Alan R. Liss, New York, 1987, p 280
Canaani D, Naiman T, Teitz T, Berg P: Immortalization of xeroderma pigmentosum cells by simian virus 40 DNA having a defective origin of DNA replication. Somat Cell Molecul Genet 12: 13–20, 1986
Brown KW, Gallimore PH: Malignant progression of an SV40-transformed human epidermal keratinocyte cell line. Br J Cancer 56: 545–554, 1987
Berry RD, Powell SC, Paraskeva C: In vitro culture of human foetal colonic epitheliall cells and their transformation with origin minus SV40 DNA. Br J Cancer 57: 287–289, 1988
Major EO, Miller AE, Mourrain P, TTraub RE, de Widt E, Sever J: Establishment of a line of fetal glial cells that supports JC virus multiplication. Proc Natl Acad Sci 82: 1257–1261, 1985
Rauth AM, Mohindra JK: Selective toxicity of 5-(3,3-dimethyl 1–1-triazeno)imidazole-4-carboxamide towards hypoxic mammalian cells. Cancer Res 41: 4900–4905, 1981
Michler-Stuke A, Bottenstein JE: Defined media for the grwth of human and rat glial-derived cells. Cold Spring Harbor Conf Cell Proliferation 9: 959–971, 1982
Thomson JE, Rauth AM: An in vitro assay to measure the viability of KHT tumor cells not previously exposed to culture conditions. Radiat Res 58: 262–276, 1974
Tannock IF, Choo B, Buick R: The radiation response of human bladder cancer assessed in vitro or as xenografts in immune-deprived mice. Int J Radiat Oncol Biot Phys 10: 1897–1902, 1984
Robinson G: Immunohistochemistry. In: Bancroft JD and Stevens A (eds) Theory and Practice of Histological Techniques. Churchill Livingstone, Edinburgh, 1982, pp 406–427
Bigner DD, Bigner SH, Ponten J, Westermark B, Mahaley MS, Ruoslahti E, Herschman H, Eng LF, Wikstrand CJ: Heterogeneity of genotypic and phenotypic characteristics of fifteen permanent cell lines derived from human gliomas. J Neuropathol Exp Neurol 40: 201–229, 1981
Harlow E, Crawford LV, Pim DC, Williamson NM: Monoclonal antibodies specific for simian virus 40 tumor antigens. J Virol 39: 861–869, 1981
Rovinski B, Munroe D, Peacock J, Mowat M, Bernstein A, Benchimol S: Deletion of 5′-coding sequences of the cellular P53 gene in mouse erythroleukaemia: a novel mechanism of oncogene regulation. Mol Cell Biol 7: 847–853, 1987
Gluzman Y, Frisque RJ, Sambrook J: Origin-defective mutants of SV40. Cold Spring Harbor Symp Quant Biol 44: 293–300, 1980
Helinski DR: Plasmids as vectors for gene cloning. In: Hollaender A, Burris RH, Day PR, Hardy RWF, Helinski DR, Lamborg MR, Owens L, Valentine RC (eds) Genetic Engineering for Nitrogen Fixation. Plenum Press, New York, 1977, pp 19–49
Gluzman Y, Sambrook JF, Frisque RF: Expression of early genes of origin defective mutants of simian virus 40. Proc Natl Acad Sci 77: 3898–3902, 1980
Stein GH: T98G: An anchorage-independent human tumor cell line that exhibits stationary phase Gl arrest in vitro. Cell Physiol 99: 43–54, 1979
Nister M, Wedell B, Betsholtz C, Bywater M, Pettersson M, Westermark B, Mark J: Evidence for progressional changes in the human glioma line U-343 MGa: Analysis of karyotype and expression of genes encoding the subunit chains of platelet derived growth factor. Cancer Res 47: 4953–4960, 1987
Sack GH: Human cell transformation by simian virus 40 — a review. In vitro 17: 1–19, 1981
Bigner SH, Mark J, Burger PC, Mahaley MS, Bullard DE, Muhlbaier LH, Bigner DD: Specific chromosomal abnormalities in malignant human gliomas. Cancer Res 48: 405–411, 1988
Gibas Z, Becher R, Kawinski E, Horoszewicz J, Sandberg AA: A high-resolution study of chromosome changes in a human prostatic carcinoma cell line (LNCaP). Cancer Genet Cytogenet 11: 399–404, 1984
Pittman S, Russell PJ, Jelbart ME, Wass J, Raghaven D: Flow cytometric and karyotypic analysis of a primary small cell carcinoma of the prostate: a xenografted cell line. Cancer Genet Cytogenet 26: 165–169, 1987
Friend SH, Dryja TP, Weinberg RA: Oncogenes and tumor-suppressing genes. New Engl J Med 318: 618–622, 1988
Kinzler KW, Bigner SH, Bigner DD, Trent JM, Law ML, O'Brien SJ, Wong AJ, Vogelstein B: Identification of an amplified, highly expressed gene in a human glioma. Science 236: 70–73, 1987
Ruddon RW: Cancer Biology. Oxford University Press, Oxford, 1987, p 192
Watson JD, Hopkins NH, Roberts JW, Steitz JA, Weiner AM: Molecular Biology of the Gene Vol II. Benjamin/Cummings, California, 1987, p 1022
Gluzman Y, Ahrens B: SV40 early mutants that are defective for viral synthesis but competent for transformation of cultured rat and simian cells. Virology 123: 78–92, 1982
Bigner SH, Bullard DE, Pegram CN, Wikstrand CJ, Bigner DD: Relationship of in vitro morphologic and growth characteristics of established human glioma-derived cell lines to their tumorigenicity in athymic nude mice. J Neuropathol Exp Neurol 40: 390–409, 1981
Steinert PM, Jones JCR, Goldman RB: Intermediate filaments. J Cell Biol 99: 22s–27s, 1984
Bigner SH, Mark J, Bigner DD: Chromosomal progression of malignant human gliomas from biopsy to establishment as permanent lines in vitro. Cancer Genet Cytogenet 24: 163–176, 1987
Franks AJ, Burrow HM: In vitro heterogeneity in human gliomas. Are all transformed cells of glial origin? Anticancer Res 6: 625–630, 1986
Rutka JT, Giblin JR, Balkissoon R, Wen D, Myatt CA, McCulloch ML, Rosenblum ML: Characterization of fetal human brain cultures. Dev Neurosci 9: 154–173, 1987
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Davey, P., Rauth, A.M., Mason, L. et al. Spontaneous phenotypic and karyotypic progression in the SV40 transfected cell line SVG during prolonged passage in vitro . J Neuro-Oncol 8, 13–22 (1990). https://doi.org/10.1007/BF00182082
Issue Date:
DOI: https://doi.org/10.1007/BF00182082