Abstract
Epidermal cell clones able to proliferate under conditions that cause normal human foreskin keratinocytes (NHK) to terminally differentiate were obtained in a dose-dependent fashion after repeated x-irradiation. No terminal differentiation-resistant (TDR) clones were detected unless the total x-ray dose was split in several fractions given at protracted intervals. The x-ray-induced TDR cells were aneuploid and differed from growing NHK with regard to expression of specific protein markers of differentiation. One of the isolated TDR clones escaped senescence but failed to form tumors in nude mice. Altogether, these data indicate that NHK cultures can be used to quantitate phenotypic changes associated with neoplastic transformation of normal human epithelial cells upon exposure to defined regimens of physicochemical treatments.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Baden H. P., Kubilus J., Kvedar J. C., Steinberg M. L., Wolman S. R. Isolation and characterization of a spontaneously arising long-lived line of human keratinocytes (NM 1). In Vitro Cell Dev Biol. 1987 Mar;23(3):205–213. doi: 10.1007/BF02623581. [DOI] [PubMed] [Google Scholar]
- Borek C. Radiation oncogenesis in cell culture. Adv Cancer Res. 1982;37:159–232. doi: 10.1016/s0065-230x(08)60884-2. [DOI] [PubMed] [Google Scholar]
- Boukamp P., Petrussevska R. T., Breitkreutz D., Hornung J., Markham A., Fusenig N. E. Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line. J Cell Biol. 1988 Mar;106(3):761–771. doi: 10.1083/jcb.106.3.761. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Buidin R., Golstein J., Parent D., Heenen M. Detection of a heterogeneity of basal keratinocytes in human hyperpapillomatous epidermis: a monoclonal antibody study. Arch Dermatol Res. 1988;280(1):64–66. doi: 10.1007/BF00412693. [DOI] [PubMed] [Google Scholar]
- Cairns J. Mutation selection and the natural history of cancer. Nature. 1975 May 15;255(5505):197–200. doi: 10.1038/255197a0. [DOI] [PubMed] [Google Scholar]
- Clarke R. H., Southwood T. R. Risks from ionizing radiation. Nature. 1989 Mar 16;338(6212):197–198. doi: 10.1038/338197a0. [DOI] [PubMed] [Google Scholar]
- Hawley-Nelson P., Vousden K. H., Hubbert N. L., Lowy D. R., Schiller J. T. HPV16 E6 and E7 proteins cooperate to immortalize human foreskin keratinocytes. EMBO J. 1989 Dec 1;8(12):3905–3910. doi: 10.1002/j.1460-2075.1989.tb08570.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heidelberger C., Freeman A. E., Pienta R. J., Sivak A., Bertram J. S., Casto B. C., Dunkel V. C., Francis M. W., Kakunaga T., Little J. B. Cell transformation by chemical agents--a review and analysis of the literature. A report of the U.S. Environmental Protection Agency Gene-Tox Program. Mutat Res. 1983 Apr;114(3):283–385. doi: 10.1016/0165-1110(83)90036-2. [DOI] [PubMed] [Google Scholar]
- Kamata N., Chida K., Rikimaru K., Horikoshi M., Enomoto S., Kuroki T. Growth-inhibitory effects of epidermal growth factor and overexpression of its receptors on human squamous cell carcinomas in culture. Cancer Res. 1986 Apr;46(4 Pt 1):1648–1653. [PubMed] [Google Scholar]
- McCormick J. J., Maher V. M. Malignant transformation of mammalian cells in culture, including human cells. Environ Mol Mutagen. 1989;14 (Suppl 16):105–113. doi: 10.1002/em.2850140619. [DOI] [PubMed] [Google Scholar]
- Morris A., Steinberg M. L., Defendi V. Keratin gene expression in simian virus 40-transformed human keratinocytes. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8498–8502. doi: 10.1073/pnas.82.24.8498. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Namba M., Nishitani K., Fukushima F., Kimoto T. Multistep carcinogenesis of normal human fibroblasts. Human fibroblasts immortalized by repeated treatment with Co-60 gamma rays were transformed into tumorigenic cells with Ha-ras oncogenes. Anticancer Res. 1988 Sep-Oct;8(5A):947–958. [PubMed] [Google Scholar]
- Pirisi L., Yasumoto S., Feller M., Doniger J., DiPaolo J. A. Transformation of human fibroblasts and keratinocytes with human papillomavirus type 16 DNA. J Virol. 1987 Apr;61(4):1061–1066. doi: 10.1128/jvi.61.4.1061-1066.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rheinwald J. G., Beckett M. A. Tumorigenic keratinocyte lines requiring anchorage and fibroblast support cultured from human squamous cell carcinomas. Cancer Res. 1981 May;41(5):1657–1663. [PubMed] [Google Scholar]
- Rheinwald J. G., Green H. Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. Cell. 1975 Nov;6(3):331–343. doi: 10.1016/s0092-8674(75)80001-8. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Seabright M. The use of proteolytic enzymes for the mapping of structural rearrangements in the chromosomes of man. Chromosoma. 1972;36(2):204–210. doi: 10.1007/BF00285214. [DOI] [PubMed] [Google Scholar]
- Stampfer M. R., Bartley J. C. Induction of transformation and continuous cell lines from normal human mammary epithelial cells after exposure to benzo[a]pyrene. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2394–2398. doi: 10.1073/pnas.82.8.2394. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Su Z. Z., Luo Z. Y., Guo L. P., Dupont F., Avalosse B., Rommelaere J. Positive selection of human cells lacking several transformation parameters from an SV40-transformed culture by means of parvovirus H-1. Carcinogenesis. 1988 Aug;9(8):1395–1400. doi: 10.1093/carcin/9.8.1395. [DOI] [PubMed] [Google Scholar]
- Sutherland B. M., Cimino J. S., Delihas N., Shih A. G., Oliver R. P. Ultraviolet light-induced transformation of human cells to anchorage-independent growth. Cancer Res. 1980 Jun;40(6):1934–1939. [PubMed] [Google Scholar]
- Thraves P., Salehi Z., Dritschilo A., Rhim J. S. Neoplastic transformation of immortalized human epidermal keratinocytes by ionizing radiation. Proc Natl Acad Sci U S A. 1990 Feb;87(3):1174–1177. doi: 10.1073/pnas.87.3.1174. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsao M. C., Walthall B. J., Ham R. G. Clonal growth of normal human epidermal keratinocytes in a defined medium. J Cell Physiol. 1982 Feb;110(2):219–229. doi: 10.1002/jcp.1041100217. [DOI] [PubMed] [Google Scholar]
- Vassart G., Georges M., Monsieur R., Brocas H., Lequarre A. S., Christophe D. A sequence in M13 phage detects hypervariable minisatellites in human and animal DNA. Science. 1987 Feb 6;235(4789):683–684. doi: 10.1126/science.2880398. [DOI] [PubMed] [Google Scholar]
- Wille J. J., Jr, Pittelkow M. R., Shipley G. D., Scott R. E. Integrated control of growth and differentiation of normal human prokeratinocytes cultured in serum-free medium: clonal analyses, growth kinetics, and cell cycle studies. J Cell Physiol. 1984 Oct;121(1):31–44. doi: 10.1002/jcp.1041210106. [DOI] [PubMed] [Google Scholar]
- Woloschak G. E., Chang-Liu C. M., Shearin-Jones P. Regulation of protein kinase C by ionizing radiation. Cancer Res. 1990 Jul 1;50(13):3963–3967. [PubMed] [Google Scholar]