Skip to main content
Gut logoLink to Gut
. 1987 Jan;28(1):33–39. doi: 10.1136/gut.28.1.33

Enteroglucagon and experimental intestinal carcinogenesis in the rat.

A P Savage, J L Matthews, M A Ghatei, T Cooke, S R Bloom
PMCID: PMC1432717  PMID: 3817582

Abstract

To assess the association between the putative intestinal trophic hormone enteroglucagon and the development of intestinal tumours, four groups of 20 rats underwent either jejunal transection or 20%, 50%, or 80% proximal small bowel resection. Tumours were induced with azoxymethane 10 mg/kg weekly for 12 weeks. At 26 weeks there was a promotion of colonic neoplasia from a median of 0.5 (range 0-3) per rat in the transection group to 1.0 (0-3) in the 50% resected group (p less than 0.01) but no significant promotion in the 80% resection group. In the small bowel, increasing resection resulted in a progressive promotion of tumours from a median of 1.0 (range 0-3) per rat in the transection group to 2.0 (0-5) in the 50% resection group (p less than 0.001) and 3.0 (0-11) in the 80% group (p less than 0.01). Plasma enteroglucagon was measured at 2, 16, and 26 weeks and was raised seven-fold in the 80% resected group (p less than 0.001). There was a significant correlation between enteroglucagon concentrations and number of duodenal tumours but not colonic tumours. Crypt cell production rate in the duodenum increased from 11.5 +/- 1.9 to 29.2 +/- 1.4 cells/crypt/h in the 80% resected group (p less than 0.001) and showed a close correlation with both enteroglucagon levels and tumour promotion in the small bowel. There were no changes in crypt cell production rate in the colon with resection. This study shows a close association between enteroglucagon concentrations, promotion of tumours and crypt cell production rate in the duodenum but not in the colon.

Full text

PDF
39

Selected References

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

  1. Bloom S. R. An enteroglucagon tumour. Gut. 1972 Jul;13(7):520–523. doi: 10.1136/gut.13.7.520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Cooke T., Kirkham N., Stainthorp D. H., Inman C., Goeting N., Taylor I. Detection of early neoplastic changes in experimentally induced colorectal cancer using scanning electron microscopy and cell kinetic studies. Gut. 1984 Jul;25(7):748–755. doi: 10.1136/gut.25.7.748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cruse J. P., Lewin M. R., Clark C. G. Corynebacterium parvum enhances colonic cancer in dimethylhydrazine-treated rats. Br J Cancer. 1978 Apr;37(4):639–643. doi: 10.1038/bjc.1978.94. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Delvaux G., Caes F., Willems G. Refeeding of fasting rats stimulates epithelial cell proliferation in the excluded colon. Gastroenterology. 1984 May;86(5 Pt 1):802–807. [PubMed] [Google Scholar]
  5. Ghatei M. A., Uttenthal L. O., Christofides N. D., Bryant M. G., Bloom S. R. Molecular forms of human enteroglucagon in tissue and plasma: plasma responses to nutrient stimuli in health and in disorders of the upper gastrointestinal tract. J Clin Endocrinol Metab. 1983 Sep;57(3):488–495. doi: 10.1210/jcem-57-3-488. [DOI] [PubMed] [Google Scholar]
  6. Gleeson M. H., Bloom S. R., Polak J. M., Henry K., Dowling R. H. Endocrine tumour in kidney affecting small bowel structure, motility, and absorptive function. Gut. 1971 Oct;12(10):773–782. doi: 10.1136/gut.12.10.773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Górnacz G. E., Al-Mukhtar M. Y., Ghatei M. A., Sagor G. R., Wright N. A., Bloom S. R. Pattern of cell proliferation and enteroglucagon response following small bowel resection in the rat. Digestion. 1984;29(2):65–72. doi: 10.1159/000199012. [DOI] [PubMed] [Google Scholar]
  8. Jacobs L. R., Bloom S. R., Dowling R. H. Response of plasma and tissue levels of enteroglucagon immunoreactivity to intestinal resection, lactation and hyperphagia. Life Sci. 1981 Nov 9;29(19):2003–2007. doi: 10.1016/0024-3205(81)90610-x. [DOI] [PubMed] [Google Scholar]
  9. Johnson L. R. The trophic action of gastrointestinal hormones. Gastroenterology. 1976 Feb;70(2):278–288. [PubMed] [Google Scholar]
  10. Martin M. S., Martin F., Michiels R., Bastien H., Justrabo E., Bordes M., Viry B. An experimental model for cancer of the colon and rectum. Intestinal carcinoma induced in the rat 1,2-dimethylhydrazine. Digestion. 1973;8(1):22–34. doi: 10.1159/000197298. [DOI] [PubMed] [Google Scholar]
  11. Nundy S., Malamud D., Obertop H., Sczerban J., Malt R. A. Onset of cell proliferation in the shortened gut. Colonic hyperplasia after ileal resection. Gastroenterology. 1977 Feb;72(2):263–266. [PubMed] [Google Scholar]
  12. Oscarson J. E., Veen H. F., Ross J. S., Malt R. A. Ileal resection potentiates 1,2-dimethylhydrazine-induced colonic carcinogenesis. Ann Surg. 1979 Apr;189(4):503–508. [PMC free article] [PubMed] [Google Scholar]
  13. Rainey J. B., Davies P. W., Williamson R. C. Relative effects of ileal resection and bypass on intestinal adaptation and carcinogenesis. Br J Surg. 1984 Mar;71(3):197–202. doi: 10.1002/bjs.1800710309. [DOI] [PubMed] [Google Scholar]
  14. Ryan G. P., Dudrick S. J., Copeland E. M., Johnson L. R. Effects of various diets on colonic growth in rats. Gastroenterology. 1979 Oct;77(4 Pt 1):658–663. [PubMed] [Google Scholar]
  15. Sagor G. R., Al-Mukhtar M. Y., Ghatei M. A., Wright N. A., Bloom S. R. The effect of altered luminal nutrition on cellular proliferation and plasma concentrations of enteroglucagon and gastrin after small bowel resection in the rat. Br J Surg. 1982 Jan;69(1):14–18. doi: 10.1002/bjs.1800690106. [DOI] [PubMed] [Google Scholar]
  16. Sagor G. R., Ghatei M. A., Al-Mukhtar M. Y., Wright N. A., Bloom S. R. Evidence for a humoral mechanism after small intestinal resection. Exclusion of gastrin but not enteroglucagon. Gastroenterology. 1983 May;84(5 Pt 1):902–906. [PubMed] [Google Scholar]
  17. Scarpello J. H., Cary B. A., Sladen G. E. Effects of ileal and caecal resection on the colon of the rat. Clin Sci Mol Med. 1978 Mar;54(3):241–249. doi: 10.1042/cs0540241. [DOI] [PubMed] [Google Scholar]
  18. Scudamore C. H., Freeman H. J. Effects of small bowel transection, resection, or bypass in 1,2-dimethylhydrazine-induced rat intestinal neoplasia. Gastroenterology. 1983 Apr;84(4):725–731. [PubMed] [Google Scholar]
  19. Sharp J. G., Hanson W. R., Osborne J. W. The relationship between the compensatory response in the stomach and colon and the extent of small bowel resection in the rat. Virchows Arch B Cell Pathol Incl Mol Pathol. 1983;44(3):295–304. doi: 10.1007/BF02890179. [DOI] [PubMed] [Google Scholar]
  20. Sunter J. P., Appleton D. R., Wright N. A., Watson A. J. Pathological features of the colonic tumours induced in rats by the administration of 1,2-dimethylhydrazine. Virchows Arch B Cell Pathol. 1978 Dec 21;29(3):211–223. doi: 10.1007/BF02899354. [DOI] [PubMed] [Google Scholar]
  21. Tilson M. D., Livstone E. M. Radioautography of heterotopic autografts of ileal mucosa in rats after partial enterectomy. Surg Forum. 1975;26:393–394. [PubMed] [Google Scholar]
  22. Tilson M. D., Michaud J. T., Livstone E. M. Early proliferative activity in the left colon of the rat after partial small--bowel resection. Surg Forum. 1976;27(62):445–446. [PubMed] [Google Scholar]
  23. Urban E., Starr P. E., Michel A. M. Morphologic and functional adaptations of large bowel after small-bowel resection in the rat. Dig Dis Sci. 1983 Mar;28(3):265–272. doi: 10.1007/BF01295122. [DOI] [PubMed] [Google Scholar]
  24. Williamson R. C., Bauer F. L. Evidence for an enterotropic hormone: compensatory hyperplasia in defunctioned bowel. Br J Surg. 1978 Oct;65(10):736–739. doi: 10.1002/bjs.1800651018. [DOI] [PubMed] [Google Scholar]
  25. Williamson R. C., Bauer F. L., Oscarson J. E., Ross J. S., Malt R. A. Promotion of azoxymethane-induced colonic neoplasia by resection of the proximal small bowel. Cancer Res. 1978 Oct;38(10):3212–3217. [PubMed] [Google Scholar]
  26. Williamson R. C., Bauer F. L., Terpstra O. T., Ross J. S., Malt R. A. Contrasting effects of subtotal enteric bypass, enterectomy, and colectomy on azoxymethane-induced intestinal carcinogenesis. Cancer Res. 1980 Mar;40(3):538–543. [PubMed] [Google Scholar]
  27. Williamson R. C., Buchholtz T. W., Malt R. A. Humoral stimulation of cell proliferation in small bowel after transection and resection in rats. Gastroenterology. 1978 Aug;75(2):249–254. [PubMed] [Google Scholar]
  28. Williamson R. C. Hyperplasia and neoplasia of the intestinal tract. Ann R Coll Surg Engl. 1979 Sep;61(5):341–348. [PMC free article] [PubMed] [Google Scholar]
  29. Wright N. A., Appleton D. R. The metaphase arrest technique. A critical review. Cell Tissue Kinet. 1980 Nov;13(6):643–663. doi: 10.1111/j.1365-2184.1980.tb00503.x. [DOI] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES