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Mutagenic activation ofN-nitrosobis(2-oxopropyl)amine by pancreatic juice and assessment of its ductal tumorigenicity following intraductal administration in dogs

International Journal of Pancreatology volume 20, pages 51–57 (1996)Cite this article

Summary

Conclusion

The results suggest that systemic administration (sc and ip) of BOP induces liver damage due to BOP itself and/or its metabolites which might be formed in the liver and that interaction of BOP itself in the pancreatic duct with pancreatic juice plays an important role for pancreatic duct tumorigenicity.

Methods

Mutagenic activation and pancreatic duct tumorigenicity ofN-nitrosobis (2-oxopropyl) amine (BOP) administered sc, ip, and id were studied in dogs.

Results

Following ip administration of BOP,N-nitroso (2-hydroxypropyl) (2-oxopropyl) amine (HPOP) andN-nitrosobis (2-hydroxypropyl) amine (BHP), but not BOP, were detected in pancreatic juice, while following id administration, only BOP was detected. The pancreatic juice of one dog that received 100 mg of BOP id showed positive mutagenicity towardsSalmonella typhimurium TA100, but the pancreatic juice of two dogs that received 100 mg of BOP ip was not mutagenic. BOP showed clear mutagenicity in the presence of pancreatic juice from untreated dogs, but the pancreatic juice could not activate HPOP and BHP to mutagens. BOP administered sc for 2 wk (total dose: 600 mg) induced clinical toxicity, nausea, vomiting, and loss of appetite at 10 wk. BOP administered ip for 4 mo (total dose: 2000 mg) induced liver damage at 6 mo, but no pancreatic injury. BOP administered id for 6.5 or 12 mo (total dose: 2500 or 4700 mg, respectively) induced papillary hyperplasia and dysplasia of duct epithelial cells and ductal proliferation with fibrosis.

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Affiliations

  1. The First Department of Surgery, Juntendo University School of Medicine, Tokyo, Japan

    Toshiki Kamano

  2. Radioisotope Laboratory, Gifu Pharmaceutical University, 3-1-3 Hongo, Bunkyo-ku, 113, Tokyo, Japan

    Yukio Mori & Midori Takahashi

  3. The First Department of Pathology, Juntendo University School of Medicine, Tokyo, Japan

    Koichi Suda

  4. The First Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan

    Toyohiko Uchida & Tadahiro Takada

  5. Department of Oncological Pathology, Cancer Center, Nara Medical College, Japan

    Masahiro Tsutsumi & Yoichi Konishi

Authors
  1. Toshiki Kamano
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  2. Yukio Mori
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  3. Koichi Suda
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  4. Midori Takahashi
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  5. Toyohiko Uchida
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  6. Tadahiro Takada
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  7. Masahiro Tsutsumi
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  8. Yoichi Konishi
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Kamano, T., Mori, Y., Suda, K. et al. Mutagenic activation ofN-nitrosobis(2-oxopropyl)amine by pancreatic juice and assessment of its ductal tumorigenicity following intraductal administration in dogs. International Journal of Pancreatology 20, 51–57 (1996). https://doi.org/10.1007/BF02787376

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  • DOI: https://doi.org/10.1007/BF02787376

Key Words

  • N-Nitrosobis (2-oxopropyl) amine
  • dog
  • pancreatic duct hyperplasia
  • mutagenicity
  • metabolic activation
  • pancreatic juice