Summary
Epithelial cells cultured from bovine pancreatic ducts were given a single treatment ofN-methyl-N′-nitro-N-nitrosoguanidine (MNNG). Multinucleated cells and giant cells were observed more frequently in carcinogen-treated cultures than in controls. The MNNG-treated cultures also contained a sizeable population of small, dense cells that were not observed in control cultures. At the concentration of 1.0 μg/ml, MNNG caused an initial depression in the growth rate of the cells followed by growth stimulation for several weeks. The MNNG produced chromosomal damage in the cells as indicated by the observation that a substantial proportion of carcinogen-treated cells were heteroploid and contained a high frequency of metacentric and submetacentric chromosomes and a dicentric marker chromosome. The MNNG treated and control cultures did not acquire the ability to grow in soft agar or to produce tumors after transplantation into athymic, nude mice.
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References
American Cancer Society. Cancer Statistics, 1976, CA 26: 22–23; 1976.
Wynder, E. L. An epidemiological evaluation of the causes of cancer of the pancreas. Cancer Res. 35: 2228–2233; 1975.
Parsa, I.; Marsh, W. H. Anin vitro model of pancreatic carcinoma. Am. J. Pathol. 84: 469–478; 1976.
Jones, R. T.; Barrett, L. A.; van Haaften, C.; Harris, C. C.; Trump, B. F. Carcinogenesis in the pancreas. I. Long-term explant culture of human and bovine pancreatic ducts. J. Natl. Cancer Inst. 58: 557–565; 1977.
Priester, W. A. Data from eleven United States and Canadian Colleges of veterinary medicine on pancreatic carcinoma in domestic animals. Cancer Res. 34: 1372–1375; 1974.
Jones, R. T.; Hudson, E. A.; Harris, C. C.; Trump, B. F. Ultrastructural alterations ofN-methyl-N-nitroso-N′-nitroguanidine (MNNG)-treated pancreatic ductal explants (abstr.). Proc. Am. Assoc. Cancer Res. 19: 185/47; 1978.
Stoner, G. D.; Harris, C. C.; Bostwick, D. G.; Jones, R. T.; Trump, B. F.; Kingsbury, E. W.; Fineman, E.; Newkirk, C. Isolation and characterization of epithelial cells from bovine pancreatic duct. In Vitro 14: 581–590; 1978.
Laug, W. E. Anchorage independent growth and plasminogen activator production by bovine endothelial cells (abstr.). Proc. Am. Assoc. Cancer Res. 20: 385/396; 1979.
Barile, M. F., Bodey, G. P.; Snyder, J.; Riggs, D. B.; Grabowski, M. W. Isolation ofMycoplasma orale from leukemic bone marrow and blood by direct culture. J. Natl. Cancer Inst. 36: 155–159; 1966.
Chen, T. R. In situ detection of mycoplasma contamination in cell cultures by fluorescent Hoechst 33258 stain. Exp. Cell Res. 104: 255–262; 1977.
Barile, M. F.; Del Giudice, R. A.; Carski, T. R.; Gibbs, C. J.; Morris, J. A. Isolation and characterization ofMycoplasma arginini. Proc. Soc. Exp. Biol. Med. 129: 489–494; 1968.
Lavappa, K. S. Trypsin-Giemsa banding procedure for chromosome preparations for cultured mammalian cells. TCA Manual 4: 761–764; 1978.
MacPherson, I.; Montagnier, L. Agar suspension culture for the selective assay of cells transformed by polyoma virus. Virology 23: 291–294; 1964.
Flanagan, S. P. Nude, a new hairless gene with pleitropic effects in the mouse. Genet. Res. 8: 295–309; 1966.
Katsuta, H.; Takaoka, T. Carcinogenesis in tissue culture. XIV. Malignant transformation of rat liver parenchymal cells treated with 4-nitroquinoline 1-oxide in tissue culture. J. Natl. Cancer Inst. 49: 1563–1576; 1972.
Brown, A. M. In vitro transformation of submandibular gland epithelial cells and fibroblasts of adult rats by methylcholanthrene. Cancer Res. 33: 2779–2789; 1973.
Hashimoto, Y.; Kitagawa, S. In vitro neoplastic transformation of epithelial cells of rat urinary bladder by nitrosamines. Nature 252: 497–499; 1974.
Freeman, A. E.; Lake, R. S.; Igel, H. J.; Gernand, L.; Pezzutti, M. R.; Malone, J. M.; Mark, C.; Benedict, W. F. Heteroploid conversion of human skin cells by methylcholanthrene. Proc. Natl. Acad. Sci. U.S.A. 74: 2451–2455; 1977.
DiPaolo, J. A.; Popescu, N. C. Relationship of chromosome changes to neoplastic cell transformation. Am. J. Pathol. 85: 709–725; 1976.
Kakunaga, T. Neoplastic transformation of human diploid fibroblast cells by chemical carcinogens. Proc. Natl. Acad. Sci. U.S.A. 75: 1334–1338; 1978.
Hart, R. W.; Setlow, R. B. Correlation between deoxyribonucleic acid excision-repair and lifespan in a number of mammalian species. Proc. Natl. Acad. Sci. U. S. A. 71: 2169–2173; 1974.
Hodges, G. M.; Hicks, R. M.; Spacey, G. D. Epithelial-stromal interactions in normal and chemical carcinogen-treated adult bladder. Cancer Res. 37: 3720–3730; 1977.
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This work was supported in part by Public Health Service Contract and Interagency Agreement Y01-CP60204 from the Division of Cancer Cause and Prevention, National Cancer Institute.
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Katoh, Y., Stoner, G.D., Bostwick, D.G. et al. Morphological, growth, and chromosomal changes in bovine pancreatic duct epithelial cells exposed toN-methyl-N′-nitro-N-nitrosoguanidine. In Vitro 16, 791–796 (1980). https://doi.org/10.1007/BF02619314
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DOI: https://doi.org/10.1007/BF02619314