Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1992 Jul;66(1):46–50. doi: 10.1038/bjc.1992.214

Role of cholecystokinin in dietary fat-promoted azaserine-induced pancreatic carcinogenesis in rats.

M J Appel 1, M Meijers 1, A Van Garderen-Hoetmer 1, C B Lamers 1, L C Rovati 1, D Sprij-Mooij 1, J B Jansen 1, R A Woutersen 1
PMCID: PMC1977907  PMID: 1637675

Abstract

The role of cholecystokinin in dietary fat-promoted pancreatic carcinogenesis was investigated in azaserine-treated rats, using lorglumide, a highly specific cholecystokinin-receptor antagonist. The animals were killed 8 months after the start of treatment. Cholecystokinin, but not dietary unsaturated fat, increased pancreatic weight. Rats treated with cholecystokinin developed more acidophilic atypical acinar cell nodules, adenomas and adenocarcinomas than control animals. Rats maintained on the high-fat diet developed significantly more adenomas and adenocarcinomas than controls given a diet low in unsaturated fat. Lorglumide largely inhibited the enhancing effect of cholecystokinin, but not of dietary fat, on pancreatic carcinogenesis indicating that it is unlikely that the promoting effect of dietary unsaturated fat on pancreatic carcinogenesis is mediated via cholecystokinin.

Full text

PDF
46

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beardshall K., Frost G., Morarji Y., Domin J., Bloom S. R., Calam J. Saturation of fat and cholecystokinin release: implications for pancreatic carcinogenesis. Lancet. 1989 Oct 28;2(8670):1008–1010. doi: 10.1016/s0140-6736(89)91017-9. [DOI] [PubMed] [Google Scholar]
  2. Birt D. F., Salmasi S., Pour P. M. Enhancement of experimental pancreatic cancer in Syrian golden hamsters by dietary fat. J Natl Cancer Inst. 1981 Dec;67(6):1327–1332. [PubMed] [Google Scholar]
  3. Douglas B. R., Woutersen R. A., Jansen J. B., Rovati L. C., Lamers C. B. Comparison of the effect of lorglumide on pancreatic growth stimulated by camostate in rat and hamster. Life Sci. 1990;46(4):281–286. doi: 10.1016/0024-3205(90)90034-o. [DOI] [PubMed] [Google Scholar]
  4. Douglas B. R., Woutersen R. A., Jansen J. B., Rovati L. C., Lamers C. B. Study into the role of cholecystokinin in bombesin-stimulated pancreatic growth in rats and hamsters. Eur J Pharmacol. 1989 Feb 28;161(2-3):209–214. doi: 10.1016/0014-2999(89)90845-5. [DOI] [PubMed] [Google Scholar]
  5. Douglas B. R., Woutersen R. A., Jansen J. B., de Jong A. J., Lamers C. B. The influence of different nutrients on plasma cholecystokinin levels in the rat. Experientia. 1988 Jan 15;44(1):21–23. doi: 10.1007/BF01960229. [DOI] [PubMed] [Google Scholar]
  6. Douglas B. R., Woutersen R. A., Jansen J. B., de Jong A. J., Rovati L. C., Lamers C. B. Influence of cholecystokinin antagonist on the effects of cholecystokinin and bombesin on azaserine-induced lesions in rat pancreas. Gastroenterology. 1989 Feb;96(2 Pt 1):462–469. doi: 10.1016/0016-5085(89)91572-2. [DOI] [PubMed] [Google Scholar]
  7. Douglas B. R., Woutersen R. A., Jansen J. B., de Jong A. J., Rovati L. C., Lamers C. B. Modulation by CR-1409 (lorglumide), a cholecystokinin receptor antagonist, of trypsin inhibitor-enhanced growth of azaserine-induced putative preneoplastic lesions in rat pancreas. Cancer Res. 1989 May 1;49(9):2438–2441. [PubMed] [Google Scholar]
  8. Gordis L., Gold E. B. Epidemiology of pancreatic cancer. World J Surg. 1984 Dec;8(6):808–821. doi: 10.1007/BF01656020. [DOI] [PubMed] [Google Scholar]
  9. Karmali R. A. Prostaglandins and cancer. CA Cancer J Clin. 1983 Nov-Dec;33(6):322–332. doi: 10.3322/canjclin.33.6.322. [DOI] [PubMed] [Google Scholar]
  10. Lin R. S., Kessler I. I. A multifactorial model for pancreatic cancer in man. Epidemiologic evidence. JAMA. 1981 Jan 9;245(2):147–152. [PubMed] [Google Scholar]
  11. Longnecker D. S., Roebuck B. D., Curphey T. J., Lhoste E., Coon C. I., MacMillan D. Effects of corn oil and benzyl acetate on number and size of azaserine-induced foci in the pancreas of LEW and F344 rats. Environ Health Perspect. 1986 Sep;68:197–201. doi: 10.1289/ehp.8668197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. MacMahon B. Risk factors for cancer of the pancreas. Cancer. 1982 Dec 1;50(11 Suppl):2676–2680. [PubMed] [Google Scholar]
  13. Makovec F., Bani M., Cereda R., Chisté R., Pacini M. A., Revel L., Rovati L. A., Rovati L. C., Setnikar I. Pharmacological properties of lorglumide as a member of a new class of cholecystokinin antagonists. Arzneimittelforschung. 1987 Nov;37(11):1265–1268. [PubMed] [Google Scholar]
  14. Makovec F., Chistè R., Bani M., Pacini M. A., Setnikar I., Rovati L. A. New glutaramic acid derivatives with potent competitive and specific cholecystokinin-antagonistic activity. Arzneimittelforschung. 1985;35(7):1048–1051. [PubMed] [Google Scholar]
  15. Meijers M., van Garderen-Hoetmer A., Lamers C. B., Rovati L. C., Jansen J. B., Woutersen R. A. Role of cholecystokinin in the development of BOP-induced pancreatic lesions in hamsters. Carcinogenesis. 1990 Dec;11(12):2223–2226. doi: 10.1093/carcin/11.12.2223. [DOI] [PubMed] [Google Scholar]
  16. Pour P. M., Lawson T., Helgeson S., Donnelly T., Stepan K. Effect of cholecystokinin on pancreatic carcinogenesis in the hamster model. Carcinogenesis. 1988 Apr;9(4):597–601. doi: 10.1093/carcin/9.4.597. [DOI] [PubMed] [Google Scholar]
  17. Rao M. S., Upton M. P., Subbarao V., Scarpelli D. G. 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. 1982 May;46(5):527–534. [PubMed] [Google Scholar]
  18. Roebuck B. D., Kaplita P. V., Edwards B. R., Praissman M. Effects of dietary fats and soybean protein on azaserine-induced pancreatic carcinogenesis and plasma cholecystokinin in the rat. Cancer Res. 1987 Mar 1;47(5):1333–1338. [PubMed] [Google Scholar]
  19. Roebuck B. D., Yager J. D., Jr, Longnecker D. S. Dietary modulation of azaserine-induced pancreatic carcinogenesis in the rat. Cancer Res. 1981 Mar;41(3):888–893. [PubMed] [Google Scholar]
  20. Roebuck B. D., Yager J. D., Jr, Longnecker D. S., Wilpone S. A. Promotion by unsaturated fat of azaserine-induced pancreatic carcinogenesis in the rat. Cancer Res. 1981 Oct;41(10):3961–3966. [PubMed] [Google Scholar]
  21. Scherer E. Use of a programmable pocket calculator for the quantitation of precancerous foci. Carcinogenesis. 1981;2(8):805–807. doi: 10.1093/carcin/2.8.805. [DOI] [PubMed] [Google Scholar]
  22. Smith J. P., Kramer S., Bagheri S. Effects of a high-fat diet and L364,718 on growth of human pancreas cancer. Dig Dis Sci. 1990 Jun;35(6):726–732. doi: 10.1007/BF01540175. [DOI] [PubMed] [Google Scholar]
  23. Woutersen R. A., van Garderen-Hoetmer A., Bax J., Feringa A. W., Scherer E. Modulation of putative preneoplastic foci in exocrine pancreas of rats and hamsters. I. Interaction of dietary fat and ethanol. Carcinogenesis. 1986 Sep;7(9):1587–1593. doi: 10.1093/carcin/7.9.1587. [DOI] [PubMed] [Google Scholar]
  24. Woutersen R. A., van Garderen-Hoetmer A., Bax J., Scherer E. Modulation of dietary fat-promoted pancreatic carcinogenesis in rats and hamsters by chronic coffee ingestion. Carcinogenesis. 1989 Feb;10(2):311–316. doi: 10.1093/carcin/10.2.311. [DOI] [PubMed] [Google Scholar]
  25. Woutersen R. A., van Garderen-Hoetmer A. Inhibition of dietary fat-promoted development of (pre)neoplastic lesions in exocrine pancreas of rats and hamsters by supplemental vitamins A, C and E. Cancer Lett. 1988 Aug 15;41(2):179–189. doi: 10.1016/0304-3835(88)90114-0. [DOI] [PubMed] [Google Scholar]
  26. Wynder E. L., Mabuchi K., Maruchi N., Fortner J. G. Epidemiology of cancer of the pancreas. J Natl Cancer Inst. 1973 Mar;50(3):645–667. doi: 10.1093/jnci/50.3.645. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES