International Journal of Pancreatology

, Volume 16, Issue 2–3, pp 171–177 | Cite as

Characterization of three cloned cell lines from aN-nitrosobis(2-hydroxypropyl)amine-induced transplantable hamster pancreatic ductal adenocarcinoma

  • Toshio Mori
  • Masahiro Tsutsumi
  • Osamu Noguchi
  • Kohsuke Horiguchi
  • Kanya Hohnoki
  • Shunji Okita
  • Fumio Suzuki
  • Yoichi Konishi


To investigate characteristics of pancreatic carcinoma growth behavior, the cloned cell lines, HPD1NR, HPD2NR, and HPD3NR, were established from a transplantable hamster ductal adenocarcinoma induced byN-nitrosobis(2-hydroxypropyl)amine (BHP). All three clones showed similar epithelial cell morphology and grew as sheets in culture with no differences in doubling times, ranging from 23-28 h. Mutation in the c-Ki-ras exon 1 was detected in common. The modal chromosome numbers were also found to be similar at 60, 62, and 60-62 in the less than tetraploid cells in the three clones. In contrast, a clear difference in frequencies of tetraploid or polyploid cells at 24.7, 22.5, and 75.5% in HPD1NR, HPD2NR, and HPD3NR, respectively, was evident. Tumorigenic potency evaluated by transplanting individual clones revealed HPD3NR to display pronouncedly less growth in syngeneic hamsters. The results suggest that increase in frequency of tetraploid or polyploid cells might be associated with a decreased in vivo growth potential of hamster pancreatic ductal adenocarcinomas, and suggest that these clones might become a valuable tool for understanding in vivo growth mechanisms of cancer cells.

Key Words

Pancreatic ductal adenocarcinoma cell line hamster polyploidy decreased in vivo growth potential Ki-ras BHP 



ethylenediaminetetraacetic acid disodium salt




Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Knapp ML. Partial characterization of an oncofetal antigen: Its role in the differential diagnosis and therapy of patients with pancreatic cancer.Ann Clin Biochem 1981; 18: 131–143.PubMedGoogle Scholar
  2. 2.
    Health and welfare statistics in Japan. Health and welfare statistics association. 1992.Google Scholar
  3. 3.
    Pour P, Krueger FW, Althoff J, Cardesa A, Mohr U. Cancer of the pancreas induced in the Syrian golden hamster.Am J Pathol 1974; 76: 349–358.PubMedGoogle Scholar
  4. 4.
    Pour P, Althoff J, Krueger F, Schmaehl D, Mohr U. Induction of pancreatic neoplasms by 2,2′-dioxopropyl-N propylnitrosamine.Cancer Lett 1975; 1: 3–6.PubMedCrossRefGoogle Scholar
  5. 5.
    Pour PM, Runge RG, Birt D, Gingell R, Lawson T, Nagel D, Wallcave L, Salmasi SZ. Current knowledge of pancreatic carcinogenesis in the hamster and its relevance to human cancer.Cancer 1981; 47: 1573–1587.PubMedCrossRefGoogle Scholar
  6. 6.
    Pour PM. Cell differentiation during pancreatic carcinogenesis.Scand J Gastroenterol 1988; 151: 123–130.CrossRefGoogle Scholar
  7. 7.
    Fujii H, Egami H, Chaney W, Pour P, Pelling J. Pancreatic ductal adenocarcinomas induced in Syrian hamsters byN- nitrosobis(2-oxopropyl)amine contain a c-Ki-ras oncogene with a point-mutated codon 12.Mol Carcinogenesis 1990; 3:296–301.CrossRefGoogle Scholar
  8. 8.
    Tsutsumi M, Murakami Y, Kondoh S Tsujiuchi T, Hohnoki K, Horiguchi K, Noguchi O, Kobayashi E, Okita S, Sekiya T, Konishi Y. Comparison of K-ras oncogene activation in pancreatic duct carcinomas and cholangiocarcinomas induced in hamsters byN-nitrosobis(2-hydroxypropyl) amine.Jpn J Cancer Res 1993; 84: 956–960.PubMedGoogle Scholar
  9. 9.
    Tsutsumi M, Kondoh S, Noguchi O, Horiguchi K, Kobayashi E, Okita S, Ohashi K, Honoki K, Tsujiuchi T, Konishi Y. K-ras gene mutation in early ductal lesions induced in a rapid production model for pancreatic carcinomas in Syrian hamsters.Jpn J Cancer Res 1993; 84: 1101–1105.PubMedGoogle Scholar
  10. 10.
    Cerny WL, Mangold KA, Scarpelli DG. K-ras mutation is an early event in pancreatic duct carcinogenesis in the Syrian golden hamster.Cancer Res 1992; 52: 4507–4513.PubMedGoogle Scholar
  11. 11.
    Almoguera C, Shibata D, Forrester K, Martin J, Arnheim N, Perucho M. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes.Cell 1988; 53: 549–554.PubMedCrossRefGoogle Scholar
  12. 12.
    Smit VT, Boot AJ, Smits AM, Fleuren GJ, Cornelisse CJ, Bos JL. KRAS codon 12 mutations occur very frequently in pancreatic adenocarcinomas.Nucleic Acids Res 1988; 16: 7773–7782.PubMedCrossRefGoogle Scholar
  13. 13.
    Lieber M, Mazzetta J, Walter N-R, Kaplan M, Todaro G. Establishment of a continuous tumor-cell line (PANC-1) from a human carcinoma of the exocrine pancreas.Int J Cancer 1975; 15: 741–747.PubMedCrossRefGoogle Scholar
  14. 14.
    Yunis AA, Arimura GK, Russin DJ. Human pancreatic carcinoma (MIA PaCa-2) in continuous culture: Sensitivity to asparaginase.Int J Cancer 1977; 19: 128–135.PubMedCrossRefGoogle Scholar
  15. 15.
    Grant AG, Duke D, Hermon-Taylor J. Establishment and characterization of primary human pancreatic carcinoma in continuous cell culture and in nude mice.Br J Cancer 1979; 39: 143–151.PubMedGoogle Scholar
  16. 16.
    Yamaguchi N, Uozumi M, Ikeuchi H, Morioka H, Machino M, Kawai K. Establishment and characterization of a carcinoembryonic antigen producing cell line derived from human pancreatic exocrine cancer.Gastroenterol Jpn 1983; 18: 585–592.PubMedGoogle Scholar
  17. 17.
    Kyriazis AP, McCombs III WB, Sandberg AA, Sloane NH, Lepera R. Establishment and characterization of human pancreatic adenocarcinoma cell line SW-1990 in tissue culture and the nude mouse.Cancer Res 1983; 43: 4393- 4401.PubMedGoogle Scholar
  18. 18.
    Akagi T, Kimoto T. Establishment and characteristics of a human pancreatic cancer cell line (HGC-25).Acta Path Jap 1977; 27: 51–58.PubMedGoogle Scholar
  19. 19.
    Metzgar RS, Gaillard MT, Levine SJ, Tuck FL, Bossen EH, Borowitz MJ. Antigens of human pancreatic adenocarcinoma cells defined by murine monoclonal antibodies.Cancer Res 1982; 42: 601–608.PubMedGoogle Scholar
  20. 20.
    Dexter DL, Matook GM, Meitner PA, Bogaars HA, Jolly GA, Turner MD, Calabresi P. Establishment and characterization of two human pancreatic cancer cell lines tumorigenic in athymic mice.Cancer Res 1982; 42: 2705–2714.PubMedGoogle Scholar
  21. 21.
    Okabe T, Yamaguchi N, Ohsawa N. Establishment and characterization of a carcinoembryonic antigen (CEA)-producing cell line from a human carcinoma of the exocrine pancreas.Cancer 1983; 51: 662–668.PubMedCrossRefGoogle Scholar
  22. 22.
    Tsujiuchi T, Tsutsumi M, Denda A, Amanuma T, Kondoh S, Kamino K, Konishi Y. Effect of 3-aminobenzamide on induction of multiorgan carcinogenesis byN-nitrosobis(2- hydroxypropyl)amine in hamsters.Jpn J Cancer Res 1991; 82: 793–799.PubMedGoogle Scholar
  23. 23.
    Saito S, Nishimura N, Kubota Y, Yamazaki K, Shibuya T, Sasaki H. Establishment and characterization of a cultured cell line derived from nitrosamine-induced pancreatic ductal adenocarcinoma in Syrian golden hamsters.Gastroenterol Jpn 1988; 23: 183–194.PubMedGoogle Scholar
  24. 24.
    Egami H, Takiyama Y, Cano M, Houser WH, Pour PM. Establishment of hamster pancreatic ductal carcinoma cell line (PC-1) producing blood group-related antigens.Carcinogenesis 1989; 10: 861–869.PubMedGoogle Scholar
  25. 25.
    Liang P, Pardee AB. Differential display of eukaryotic messenger RNA by means of the poly merase chain reaction.Science 1992; 257: 967–971.PubMedCrossRefGoogle Scholar
  26. 26.
    Elsasser H-P, Lehr U, Agricola B, Kern HF. Establishment and characterization of two cell lines with different grade of differentiation derived from one primary human pancreatic adenocarcinoma.Virchows Archiv B. Cell Pathol 1992; 61: 295–306.CrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 1994

Authors and Affiliations

  • Toshio Mori
    • 1
  • Masahiro Tsutsumi
    • 2
  • Osamu Noguchi
    • 2
  • Kohsuke Horiguchi
    • 2
  • Kanya Hohnoki
    • 2
  • Shunji Okita
    • 2
  • Fumio Suzuki
    • 2
  • Yoichi Konishi
    • 3
  1. 1.RI Center and Department of Oncological Pathology, Cancer CenterNara Medical UniversityKashihara, NaraJapan
  2. 2.Department of Oncological Pathology, Cancer CenterNara Medical UniversityKashihara, NaraJapan
  3. 3.Division of Radiation Biology, Faculty of Pharmaceutical SciencesKanazawa UniversityKanazawaJapan

Personalised recommendations