Skip to main content

Early Morphologic Markers of Carcinogenicity in Rat Pancreas

  • Chapter

Part of the book series: Environmental Science Research ((ESRH,volume 29))

Abstract

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.

This is a preview of subscription content, log in via an institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  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. Longnecker, D.S., and T.J. Curphey (1975) Adenocarcinoma of the pancreas in azaserine-treated rats. Cancer Res. 35:2249–2257.

    Google Scholar 

  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. 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. 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.

    Article  Google Scholar 

  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. 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.

    Article  Google Scholar 

  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. 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.

    Article  Google Scholar 

  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. 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. Longnecker, D.S. (1982) Editorial: Experimental pancreatic carcinogenesis. Lab. Invest. 46:543–544.

    Google Scholar 

  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. 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. 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.

    Article  Google Scholar 

  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. 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.

    Article  Google Scholar 

  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. 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. Schaeffer, B.K. (Pers. Comm.)

    Google Scholar 

  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. 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. Gould, M.N. (1982) Mammary gland cell-mediated mutagenesis of mammalian cells by organ-specific carcinogens. Cancer Res. 40:1836–1841.

    Google Scholar 

  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. 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. 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. Reddy, J.K., and M.S. Rao (1977) Transplantable pancreatic carcinoma of the rat. Science 198:78–80.

    Article  ADS  Google Scholar 

  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. 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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  31. Longnecker, D.S., and T.J. Curphey (Pers. Comm.)

    Google Scholar 

  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. 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. 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.

    Article  Google Scholar 

  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. Rowlatt, U., and F.J.C. Roe (1967) Epithelial tumors of the rat pancreas. J. Natl. Cancer Inst. 39:18–32.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1983 Plenum Press, New York

About this chapter

Cite this chapter

Longnecker, D.S. (1983). Early Morphologic Markers of Carcinogenicity in Rat Pancreas. In: Milman, H.A., Sell, S. (eds) Application of Biological Markers to Carcinogen Testing. Environmental Science Research, vol 29. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-3790-4_6

Download citation

  • DOI: https://doi.org/10.1007/978-1-4613-3790-4_6

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-3792-8

  • Online ISBN: 978-1-4613-3790-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics