Early Morphologic Markers of Carcinogenicity in Rat Pancreas

  • Daniel S. Longnecker
Part of the Environmental Science Research book series (ESRH, volume 29)


Carcinomas have been experimentally induced in the pancreas of rats by several chemicals since Hayashi and Hasegawa first reported induction of hyperplastic nodules and acinar cell adenomas in pancreas of rats treated with 4-hydroxyaminoquinoline-1-oxide (4-HAQO) (1). Induction of exocrine pancreatic carcinomas by azaserine, 7,12-dimethylbenz(a)anthracene, and 4-HAQO has been been studied to an extent that each can be regarded as providing a model in rats. Of these three, the azaserine-rat model has been best characterized and can be regarded as a prototype for carcinogenesis by chemicals that appear primarily to affect acinar cells and lead to their transformation. This model will be described in detail and compared with other models that will be less completely described.


Acinar Cell Acinar Cell Carcinoma Pancreatic Carcinogenesis Acinar Tissue Ethyl Diazoacetate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Hayashi, Y., and T. Hasegawa (1971) Experimental pancreatic tumor in rats after intravenous injection of 4-hydroxyaminoquinoline-l-oxide. Gann 62:329–330.Google Scholar
  2. 2.
    Longnecker, D.S., and T.J. Curphey (1975) Adenocarcinoma of the pancreas in azaserine-treated rats. Cancer Res. 35:2249–2257.Google Scholar
  3. 3.
    Lilja, H.S., E. Hyde, D.S. Longnecker, and J.D. Yager, Jr. (1977) DNA damage and repair in rat tissues following administration of azaserine. Cancer Res. 37:3925–3931.Google Scholar
  4. 4.
    Zurlo, J., T.J. Curphey, R. Hiley, and D.S. Longnecker (1982) Identification of 7-carboxymethylguanine in DNA from pancreatic acinar cells exposed to azaserine. Cancer Res. 42:1286–1288.Google Scholar
  5. 5.
    Zurlo, J., C.I. Coon, D.S. Longnecker, and T.J. Curphey (1982) Binding of14C-azaserine to DNA and protein in the rat and hamster. Cancer Lett. 16:65–70.CrossRefGoogle Scholar
  6. 6.
    Zurlo, J., B.D. Roebuck, J.V. Rutkowski, T.J. Curphey, and D.S. Longnecker (1982) Effect of pyridoxal deficiency on pancreatic DNA damage and nodule induction by azaserine. Proc. Amer. Assoc. Cancer Res. 23:68.Google Scholar
  7. 7.
    Longnecker, D.S., B.D. Roebuck, J.D. Yager, Jr., H.S. Lilja, and B. Siegmund (1981) Pancreatic carcinoma in azaserine-treated rats: Induction, classification, and dietary modulation of incidence. Cancer 47:1562–1572.CrossRefGoogle Scholar
  8. 8.
    Longnecker, D.S., J. French, E. Hyde, H.S. Lilja, and J.D. Yager, Jr. (1977) Effect of age on nodule induction by azaserine and DNA synthesis in rat pancreas. J. Natl. Cancer Inst. 58:1769–1775.Google Scholar
  9. 9.
    Konishi, Y., A. Denda, H. Maruyama, H. Yoshimura, J. Nobuoka, and M. Sunagawa (1980) Pancreatic tumors induced by a single intraperitoneal injection of azaserine in partial pancreatectomized rats. Cancer Lett. 9:43–46.CrossRefGoogle Scholar
  10. 10.
    Roebuck, B.D., and D.S. Longnecker (1977) Species and rat strain variation in pancreatic nodule induction by azaserine. J. Natl. Cancer Inst. 59:1273–1277.Google Scholar
  11. 11.
    Longnecker, D.S., and B.G. Crawford (1974) Hyperplastic nodules and adenomas of exocrine pancreas in azaserine-treated rats. J. Natl. Cancer Inst. 53:573–577.Google Scholar
  12. 12.
    Longnecker, D.S. (1982) Editorial: Experimental pancreatic carcinogenesis. Lab. Invest. 46:543–544.Google Scholar
  13. 13.
    Rao, M.S., M.P. Upton, V. Subbarao, and D.G. Scarpelli (1982) Two populations of cells with differing proliferative capacities in atypical acinar cell foci induced by 4-hydroxyaminoquinoline-1-oxide in the rat pancreas. Lab. Invest. 46:527–534.Google Scholar
  14. 14.
    Roebuck, B.D., and D.S. Longnecker. Dietary lipid promotion of azaserine-induced pancreatic tumors in the rat. In Diet and Cancer: From Basic Research to Policy Implications, D. Roe, ed. Alan R. Liss (in press).Google Scholar
  15. 15.
    Longnecker, D.S., H.S. Lilja, J.I. French, E. Kuhlmann, and W.W. Noll (1979) Transplantation of azaserine-induced carcinomas of pancreas in rats. Cancer Lett. 7:197–202.CrossRefGoogle Scholar
  16. 16.
    Rao, K.N., S. Takahashi, and H. Shinozuka (1980) Acinar cell carcinoma of the rat pancreas grown in cell culture and in nude mice. Cancer Res. 40:592–597.Google Scholar
  17. 17.
    Yager, J.D., Jr., B.D. Roebuck, J. Zurlo, D.S. Longnecker, E.O. Weselcouch, and S.A. Wilpone (1981) A single-dose protocol for azaserine initiation of pancreatic carcinogenesis in the rat. Int. J. Cancer 28:601–606.CrossRefGoogle Scholar
  18. 18.
    Roebuck, B.D., J.D. Yager, Jr., D.S. Longnecker, and S.A. Wilpone (1981) Promotion by unsaturated fat of azaserine-induced pancreatic carcinogenesis in the rat. Cancer Res. 41:3961–3966.Google Scholar
  19. 19.
    Longnecker, D.S., T.J. Curphey, E.T. Kuhlmann, and B.D. Roebuck (1982) Inhibition of pancreatic carcinogenesis by retinoids in azaserine-treated rats. Cancer Res. 42:19–24.Google Scholar
  20. 20.
    Schaeffer, B.K. (Pers. Comm.)Google Scholar
  21. 21.
    Konishi, Y., A. Denda, S. Inui, S. Takahashi, and H. Kondo (1976) Pancreatic carcinoma induced by 4-hydroxyaminoquinoline 1-oxide after partial pancreatectomy and splenectomy in rats. Gann 67:919–920.Google Scholar
  22. 22.
    Konishi, Y., A. Denda, Y. Miyata, and H. Kawabata (1976) Enhancement of pancreatic tumorigenesis of 4-hydroxyaminoquinoline 1-oxide by ethionine in rats. Gann 67:91–95.Google Scholar
  23. 23.
    Gould, M.N. (1982) Mammary gland cell-mediated mutagenesis of mammalian cells by organ-specific carcinogens. Cancer Res. 40:1836–1841.Google Scholar
  24. 24.
    Dissin, J., L.R. Mills, D.L. Mains, O. Black, and P.D. Webster (1975) Experimental induction of pancreatic adenocarcinoma in rats. J. Natl. Cancer Inst. 55:857–864.Google Scholar
  25. 25.
    Bockman, D.E., O. Black, L.R. Mills, and P.D. Webster (1978) Origin of tubular complexes developing during induction of pancreatic adenocarcinoma by 7,12-dimethylbenz(a)anthracene. Am. J. Pathol. 90:645–658.Google Scholar
  26. 26.
    Svoboda, D.J., D.L. Azarnoff (1979) Tumors in male rats fed ethyl chlorophenoxyisobutyrate, a hypolipidemic drug. Cancer Res. 39:3419–3428.Google Scholar
  27. 27.
    Reddy, J.K., and M.S. Rao (1977) Transplantable pancreatic carcinoma of the rat. Science 198:78–80.ADSCrossRefGoogle Scholar
  28. 28.
    Milman, H.A., J.M. Ward, and K.C. Chu (1978) Pancreatic carcinogenesis and naturally occurring pancreatic neoplasms of rats and mice in the NCI carcinogenesis testing program. J. Environ. Pathol. Toxicol. 1:829–840.Google Scholar
  29. 29.
    Levison, D.A., R.G.H. Morgan, J.S. Brimacombe, D. Hopwood, G. Coghill, and K.G. Wormsley (1979) Carcinogenic effects of di(2-hydroxypropyl)nitrosamine (DHPN) in male Wistar rats: Promotion of pancreatic cancer by a raw soya flour diet. Scand. J. Gastroenterol. 14:217–224.CrossRefGoogle Scholar
  30. 30.
    Longnecker, D.S., J. Zurlo, T.J. Curphey, and W.E. Adams (1982) Induction of pancreatic DNA damage and nodules in rats treated with N-nitrosobis(2-oxopropyl)amine and N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine. Carcinogenesis 3:715–717.CrossRefGoogle Scholar
  31. 31.
    Longnecker, D.S., and T.J. Curphey (Pers. Comm.)Google Scholar
  32. 32.
    Longnecker, D.S., T.J. Curphey, H.S. Lilja, J.I. French, and D.S. Daniel (1980) Carcinogenicity in rats of the nitrosourea amino acid N6-(N-methyl-N-nitrosocarbamoyl)-L-ornithine. J. Environ. Pathol. Toxicol. 4:117–129.Google Scholar
  33. 33.
    Zurlo, J., D.S. Longnecker, D.A. Cooney, E.T. Kuhlmann, and T.J. Curphey. Studies of pancreatic nodule induction and DNA damage by D-azaserine. Cancer Lett. 12:75–80.Google Scholar
  34. 34.
    Lilja, H.S., D.S. Longnecker, T.J. Curphey, D.S. Daniel, and W.E. Adams (1981) Studies of DNA damage in rat pancreas and liver by DON, ethyl diazoacetate, and azaserine. Cancer Lett. 12:139–146.CrossRefGoogle Scholar
  35. 35.
    Roebuck, B.D., and K.J. Baumgartner. Characterization of two populations of pancreatic atypical acinar cell foci induced by azaserine in the rat (in preparation).Google Scholar
  36. 36.
    Rowlatt, U., and F.J.C. Roe (1967) Epithelial tumors of the rat pancreas. J. Natl. Cancer Inst. 39:18–32.Google Scholar

Copyright information

© Plenum Press, New York 1983

Authors and Affiliations

  • Daniel S. Longnecker
    • 1
  1. 1.Department of PathologyDartmouth Medical SchoolHanoverUSA

Personalised recommendations