Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1993 May;67(5):1011–1014. doi: 10.1038/bjc.1993.185

Inhibition by amiloride of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

M Tatsuta 1, H Iishi 1, M Baba 1, H Uehara 1, A Nakaizumi 1, H Taniguchi 1
PMCID: PMC1968461  PMID: 8494694

Abstract

The effects of amiloride on the incidence and histological types of gastric cancers in Wistar rats induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and on the labelling index and proliferative fraction of gastric mucosa were investigated. After oral treatment with MNNG for 25 weeks, rats received s.c. injections of amiloride (0.25 mg kg-1 or 5.0 mg kg-1 body weight) in depot form every other day until the end of the experiment. Prolonged administration of 5.0 mg kg-1, but not 2.5 mg kg-1 of amiloride significantly decreased the incidence of gastric cancers in Week 52. However, it did not influence the histological features of the gastric cancers. It also significantly decreased the labelling index and proliferative fraction of the antral mucosa. These findings indicate that amiloride inhibits the development of gastric cancers, and that its effect may be related to its effect in decreasing cell proliferation of the antral mucosa.

Full text

PDF
1011

Selected References

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

  1. Besterman J. M., May W. S., Jr, LeVine H., 3rd, Cragoe E. J., Jr, Cuatrecasas P. Amiloride inhibits phorbol ester-stimulated Na+/H+ exchange and protein kinase C. An amiloride analog selectively inhibits Na+/H+ exchange. J Biol Chem. 1985 Jan 25;260(2):1155–1159. [PubMed] [Google Scholar]
  2. Comolli R., Zanoni L., Mauri C., Leonardi M. G. Amiloride inhibits protein synthesis and lowers the intracellular pH in exponential growing Yoshida rat ascites hepatoma (AH 130) cells: evidence for a role of the Na+/H+ exchanger. Cell Biol Int Rep. 1985 Nov;9(11):1017–1025. doi: 10.1016/0309-1651(85)90068-2. [DOI] [PubMed] [Google Scholar]
  3. Davis R. J., Czech M. P. Amiloride directly inhibits growth factor receptor tyrosine kinase activity. J Biol Chem. 1985 Feb 25;260(4):2543–2551. [PubMed] [Google Scholar]
  4. Delvaux M., Bastié M. J., Chentoufi J., Cragoe E. J., Jr, Vaysse N., Ribet A. Amiloride and analogues inhibit Na(+)-H+ exchange and cell proliferation in AR42J pancreatic cell line. Am J Physiol. 1990 Nov;259(5 Pt 1):G842–G849. doi: 10.1152/ajpgi.1990.259.5.G842. [DOI] [PubMed] [Google Scholar]
  5. Eastwood G. L., Quimby G. F. Effect of chronic cimetidine ingestion on fundic and antral epithelial proliferation in the rat. Dig Dis Sci. 1983 Jan;28(1):61–64. doi: 10.1007/BF01393362. [DOI] [PubMed] [Google Scholar]
  6. Gratzner H. G. Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine: A new reagent for detection of DNA replication. Science. 1982 Oct 29;218(4571):474–475. doi: 10.1126/science.7123245. [DOI] [PubMed] [Google Scholar]
  7. Grinstein S., Rotin D., Mason M. J. Na+/H+ exchange and growth factor-induced cytosolic pH changes. Role in cellular proliferation. Biochim Biophys Acta. 1989 Jan 18;988(1):73–97. doi: 10.1016/0304-4157(89)90004-x. [DOI] [PubMed] [Google Scholar]
  8. Häussinger D., Brodde O. E., Starke K. Alpha-adrenoceptor antagonistic action of amiloride. Biochem Pharmacol. 1987 Oct 15;36(20):3509–3515. doi: 10.1016/0006-2952(87)90333-9. [DOI] [PubMed] [Google Scholar]
  9. Iishi H., Tatsuta M., Baba M., Okuda S., Taniguchi H. Enhancement by vaso-active intestinal peptide of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats. Int J Cancer. 1992 Feb 20;50(4):649–652. doi: 10.1002/ijc.2910500428. [DOI] [PubMed] [Google Scholar]
  10. Madshus I. H. Regulation of intracellular pH in eukaryotic cells. Biochem J. 1988 Feb 15;250(1):1–8. doi: 10.1042/bj2500001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Martel P., Houdebine L. M. Effects of amiloride on the induction of DNA synthesis and casein gene expression in rabbit mammary explants. Reprod Nutr Dev. 1990;30(1):85–90. doi: 10.1051/rnd:19900108. [DOI] [PubMed] [Google Scholar]
  12. Moolenaar W. H., Tsien R. Y., van der Saag P. T., de Laat S. W. Na+/H+ exchange and cytoplasmic pH in the action of growth factors in human fibroblasts. Nature. 1983 Aug 18;304(5927):645–648. doi: 10.1038/304645a0. [DOI] [PubMed] [Google Scholar]
  13. Morstyn G., Hsu S. M., Kinsella T., Gratzner H., Russo A., Mitchell J. B. Bromodeoxyuridine in tumors and chromosomes detected with a monoclonal antibody. J Clin Invest. 1983 Nov;72(5):1844–1850. doi: 10.1172/JCI111145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Periyasamy S. M. Interaction of amiloride with alpha-adrenoreceptors: evidence from radioligand binding studies. Can J Physiol Pharmacol. 1988 May;66(5):596–600. doi: 10.1139/y88-092. [DOI] [PubMed] [Google Scholar]
  15. Presek P., Reuter C. Amiloride inhibits the protein tyrosine kinases associated with the cellular and the transforming src-gene products. Biochem Pharmacol. 1987 Sep 1;36(17):2821–2826. doi: 10.1016/0006-2952(87)90271-1. [DOI] [PubMed] [Google Scholar]
  16. Quimby G. F., Eastwood G. L. Effect of N-methyl-N'-nitro-N-nitrosoguanidine on gastroduodenal epithelial proliferation in Wistar/Lewis rats. J Natl Cancer Inst. 1981 Feb;66(2):331–337. [PubMed] [Google Scholar]
  17. Schuldiner S., Rozengurt E. Na+/H+ antiport in Swiss 3T3 cells: mitogenic stimulation leads to cytoplasmic alkalinization. Proc Natl Acad Sci U S A. 1982 Dec;79(24):7778–7782. doi: 10.1073/pnas.79.24.7778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Shi A. G., Wang Z. L., Kwan C. Y., Daniel E. E. Inhibitory effects of amiloride on alpha adrenoceptors in canine vascular smooth muscle. J Pharmacol Exp Ther. 1990 May;253(2):791–797. [PubMed] [Google Scholar]
  19. Sparks R. L., Pool T. B., Smith N. K., Cameron I. L. Effects of amiloride on tumor growth and intracellular element content of tumor cells in vivo. Cancer Res. 1983 Jan;43(1):73–77. [PubMed] [Google Scholar]
  20. Stefanini M., De Martino C., Zamboni L. Fixation of ejaculated spermatozoa for electron microscopy. Nature. 1967 Oct 14;216(5111):173–174. doi: 10.1038/216173a0. [DOI] [PubMed] [Google Scholar]
  21. Szolgay-Daniel E., Carlsson J., Zierold K., Holtermann G., Dufau E., Acker H. Effects of amiloride treatment on U-118 MG and U-251 MG human glioma and HT-29 human colon carcinoma cells. Cancer Res. 1991 Feb 1;51(3):1039–1044. [PubMed] [Google Scholar]
  22. Tatsuta M., Iishi H., Baba M. Inhibition by neostigmine and isoproterenol and promotion by atropine of experimental carcinogenesis in rat stomach by N-methyl-N'-nitro-N-nitrosoguanidine. Int J Cancer. 1989 Jul 15;44(1):188–189. doi: 10.1002/ijc.2910440134. [DOI] [PubMed] [Google Scholar]
  23. Tatsuta M., Iishi H., Baba M., Taniguchi H. Effect of 6-hydroxydopamine on gastric carcinogenesis and tetragastrin inhibition of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. Cancer Res. 1989 Aug 1;49(15):4199–4203. [PubMed] [Google Scholar]
  24. Tatsuta M., Iishi H., Baba M., Taniguchi H. Enhancement by tyrosine methyl ester of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. Int J Cancer. 1991 Jul 9;48(5):785–788. doi: 10.1002/ijc.2910480525. [DOI] [PubMed] [Google Scholar]
  25. Tatsuta M., Iishi H., Baba M., Taniguchi H. Promotion by nialamide of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. Jpn J Cancer Res. 1989 Jun;80(6):521–525. doi: 10.1111/j.1349-7006.1989.tb01670.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tatsuta M., Iishi H., Yamamura H., Baba M., Yamamoto R., Taniguchi H. Effect of cimetidine on inhibition by tetragastrin of carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. Cancer Res. 1988 Mar 15;48(6):1591–1595. [PubMed] [Google Scholar]
  27. Tutton P. J., Barkla D. H. The influence of adrenoceptor activity on cell proliferation in colonic crypt ipithelium and in colonic adenocarcinomata. Virchows Arch B Cell Pathol. 1977 Jun 24;24(2):139–146. doi: 10.1007/BF02889274. [DOI] [PubMed] [Google Scholar]
  28. Ulrich-Baker M. G., Wang P., Fitzpatrick L., Johnson L. R. Amiloride inhibits rat mucosal ornithine decarboxylase activity and DNA synthesis. Am J Physiol. 1988 Mar;254(3 Pt 1):G408–G415. doi: 10.1152/ajpgi.1988.254.3.G408. [DOI] [PubMed] [Google Scholar]
  29. Yamaguchi D. T., Sakai R., Bahn L., Cragoe E. J., Jr, Jordan S. C. Amiloride inhibition of DNA synthesis and immunoglobulin production by activated human peripheral blood mononuclear cells is independent of sodium/hydrogen antiport. J Immunol. 1986 Aug 15;137(4):1300–1304. [PubMed] [Google Scholar]
  30. Zemach L., Segal D., Shalitin Y. The interaction of amiloride with acetylcholinesterase and butyrylcholinesterase. FEBS Lett. 1990 Apr 9;263(1):166–168. doi: 10.1016/0014-5793(90)80730-7. [DOI] [PubMed] [Google Scholar]

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

RESOURCES