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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1993 Oct;84(10):1037–1042. doi: 10.1111/j.1349-7006.1993.tb02798.x

Influence of Gastric pH Modifiers on Development of Intestinal Metaplasia Induced by X‐Irradiation in Rats

Hiromitsu Watanabe 1,✉, Taro Okamoto 1, Yasuhiro Fudaba 1, Peter Osa Ogundigie 1, Akihiro Ito 1
PMCID: PMC5919052  PMID: 8226278

Abstract

The influence of gastric pH on intestinal metaplasia was examined in male Crj:CD(SD) rats. At the age of 5 weeks, animals were irradiated with two 10 Gy doses of X‐rays to the gastric region at a 3‐day interval (total 20 Gy), and 6 months after irradiation, received either secretin or histamine in silicon tubes for 2 months or had their bilateral submandibular salivary glands removed. The incidences of intestinal metaplasia in the fundus of animals after administration of secretin or histamine, or removal of the salivary glands were reduced, along with the pH values, as compared with values for rats given X‐rays alone. In both the pyloric and the fundic gland mucosae, the numbers of alkaline phosphatase (ALP)‐positive foci and type B metaplasias (intestinal crypts without Paneth cells) were also significantly decreased (P<0.01). In a second experiment, started six months after irradiation, rats were kept on 1% sodium chloride (NaCl) diet for 6 months. Subsequent removal of salivary glands along with histamine treatment brought about a marked drop in pH and in numbers of ALP‐positive foci after three and five days. The present results thus indicated that development and maintenance of intestinal metaplasia can be influenced by a decrease of pH value.

Keywords: Intestinal metaplasia, Rat, X‐ray, Gastric pH

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REFERENCES

  • 1).Jarvi , O. H. and Lauren , P.On the role of heterotopias of the intestinal epithelium in the pathogenesis of gastric cancer . Acta Pathol. Microbiol. Scand. (Suppl.) , 29 , 26 – 43 ( 1951. ). [PubMed] [Google Scholar]
  • 2).Kawachi , T. , Kogure , K. , Tanaka , N. , Tokunaga , A. , Sugimura , T. , Koyama , Y. , Kanasugi , K. , Hirota , T. and Sano , R.Studies of intestinal metaplasia in the gastric mucosa by detection of disaccharidases with “Test‐Tape” . J. Natl. Cancer Inst. , 53 , 19 – 30 ( 1974. ). [PubMed] [Google Scholar]
  • 3).Lev , R.The mucin histochemistry of normal and neoplastic gastric mucosa . Lab. Invest. , 14 , 2080 – 2100 ( 1965. ). [PubMed] [Google Scholar]
  • 4).Mangus , H. A.Observations on the presence of intestinal metaplasia with gastric mucosa . J. Pathol Bacteriol. , 44 , 389 – 398 ( 1937. ). [Google Scholar]
  • 5).Morson , B. C.Carcinoma arising from areas of intestinal metaplasia in the gastric mucosa . Br. J. Cancer , 9 , 377 – 385 ( 1955. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6).Nakamura , K. , Sugano , H. and Takagi , K.Carcinoma of the stomach in incipient phase: its histogenesis and histological appearances . Gann , 59 , 251 – 258 ( 1968. ). [PubMed] [Google Scholar]
  • 7).Matsukura , N. , Itabashi , M. , Kawachi , T. , Hirota , T. and Sugimura , T.Sequential studies on the histogenesis of gastric carcinoma in rats by weak gastric carcinogen N‐propyl‐N'‐nitro‐N‐nitrosoguanidine . J. Cancer Res. Clin. Oncol. , 98 , 153 – 163 ( 1980. ). [DOI] [PubMed] [Google Scholar]
  • 8).Matsukura , N. , Kawachi , T. , Sasajima , K. , Sano , T. , Sugimura , T. and Hirota , T.Induction of intestinal metaplasia in the stomach of rats by N‐ethyl‐N'‐nitro‐N‐nitrosoguanidine . J. Natl. Cancer Inst. , 61 , 141 – 144 ( 1978. ). [DOI] [PubMed] [Google Scholar]
  • 9).Sasajima , K. , Kawachi , T. , Matsukura , N. , Sano , T. and Sugimura , T.Intestinal metaplasia and adenocarcinoma induced in the stomach of rats by N‐propyl‐N'‐nitro‐N‐nitrosoguanidine . J. Cancer Res. Clin. Oncol. , 94 , 201 – 206 ( 1979. ). [DOI] [PubMed] [Google Scholar]
  • 10).Sugimura , T. , Fujimura , S. and Baba , T.Tumor production in the glandular stomach and alimentary tract of the rat by N‐methyl‐N'‐nitro‐N‐nitrosoguanidine . Cancer Res. , 30 , 455 – 465 ( 1970. ). [PubMed] [Google Scholar]
  • 11).Tatematsu , M. , Furihata , C. , Katsuyama , T. , Hasegawa , R. , Nakanowatari , J. , Saito , D. , Takahashi , M. , Matsushima , T. and Ito , N.Independent induction of intestinal metaplasia and gastric cancer in rats treated with N‐methyl‐N'‐nitro‐N‐nitrosoguanidine . Cancer Res. , 43 , 1335 – 1341 ( 1983. ). [PubMed] [Google Scholar]
  • 12).Watanabe , H.Experimentally induced intestinal metaplasia in Wistar rats by X‐ray irradiation . Gastroenterology , 75 , 796 – 799 ( 1979. ). [PubMed] [Google Scholar]
  • 13).Watanabe , H. , Fujii , I. and Terada , Y.Induction of intestinal metaplasia in rat gastric mucosa by local X‐irradiation . Pathol. Res. Pract. , 170 , 104 – 114 ( 1980. ). [DOI] [PubMed] [Google Scholar]
  • 14).Watanabe , H. , Nakagawa , Y. and Ito , A.Induction of gastric tumor and intestinal metaplasia in rats exposed to localized X‐irradiation of the gastric region . Jpn. J. Cancer Res. , 78 , 27 – 31 ( 1987. ). [PubMed] [Google Scholar]
  • 15).Watanabe , H. , Kamikawa , M. , Nakagawa , Y. , Takahashi , T. and Ito , A.The effects of ranitidine and cysteamine on intestinal metaplasia induced by X‐irradiation in rats . Acta Pathol. Jpn. , 38 , 1285 – 1290 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 16).Watanabe , H. , Okamoto , T. , Takahashi , T. , Ogundigie , P. O. and Ito , A.The effects of sodium chloride, miso or ethanol on development of intestinal metaplasia after X‐irradiation of the rat glandular stomach . Jpn. J. Cancer Res. , 83 , 1267 – 1272 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17).Fujii , I. , Watanabe , H. , Terada , Y. , Naito , Y. , Naito , M. and Ito , A.Induction of intestinal metaplasia in the glandular stomach of rats by X‐irradiation prior to oral administration of N‐methyl‐N'‐nitro‐N‐nitrosoguanidine . Gann , 71 , 804 – 810 ( 1980. ). [PubMed] [Google Scholar]
  • 18).Nagayo , T. , Ito , M. , Yamada , S. and Kitagawa , T.Induction of carcinoma of the glandular stomach in rats by combined treatment of feeding of N, N'‐2,7‐fluorenyl‐enebisacetamide and X‐ray irradiation to the target organs . Gann Monogr. , 8 , 305 – 315 ( 1970. ). [Google Scholar]
  • 19).Watanabe , H. and Ito , A.Relationship between gastric tumorigenesis and intestinal metaplasia in rats given X‐radiation and/or N‐methyl‐N'‐nitro‐N‐nitrosoguanidine . J. Natl. Cancer Inst. , 76 , 865 – 870 ( 1986. ). [PubMed] [Google Scholar]
  • 20).Watanabe , H. , Hirose , F. , Takizawa , S. , Terada , Y. and Fujii , I.Morphological and biochemical changes in the gastric mucosa of A/HeJ mice injected with a xenogeneic stomach antigen . Acta Pathol. Jpn. , 27 , 869 – 876 ( 1977. ). [DOI] [PubMed] [Google Scholar]
  • 21).Fujii , I. , Watanabe , H. , Naito , M. and Ito , A.The induction of intestinal metaplasia in rats by pyloroplasty or pyloroplasty plus vagotomy . Pathol. Res. Pract. , 180 , 502 – 505 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 22).Daly , M. J. , Humphray , J. M. and Stables , R.Inhibition of gastric acid secretion in the dog by the H2‐receptor antagonists, ranitidine, cimetidine, and metiamine . Gut , 21 , 408 – 412 ( 1980. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23).Hirschowitz , B. I. , Danilewitz , M. and Molina , E.Inhibition of basal acid, chloride, and pepsin secretion in duodenal ulcer by graded doses of ranitidine and atrophine with studies of pharmacokinetics of ranitidine . Gastroenterology , 82 , 1314 – 1326 ( 1982. ). [PubMed] [Google Scholar]
  • 24).Sewing , K‐F. R. , Billian , A. and Malchow , H.Comparative study with ranitidine and cimetidine on gastric secretion in normal volunteers . Gut , 21 , 750 – 752 ( 1980. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25).Walt , R. P. , Male , P‐J. , Rawlings , J. , Hunt , R. H. , Milton‐Thompson , J. G. and Misiewicz , J. J.Comparison of the effects of ranitidine, cimetidine and placebo on the 24 hour intragastric acidity and nocturnal acid secretion in patients with duodenal ulcer . Gut , 21 , 49 – 54 ( 1981. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26).Mohammed , R. , Holden , R. J. , Hearns , J. B. , Hearns , J. B. , McKibben , B. M. , Buchanan , K. D. and Crean , G. P.Effects of eight weeks' continuous treatment with oral ranitidine and cimetidine on gastric acid secretion, pepsin secretion, and fasting serum gastrin . Gut , 24 , 61 – 66 ( 1983. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27).Groves , W. G. , Schlosser , J. H. and Mead , F. D.Acid hypersecretion and duodenal ulcers produced by cysteamine in rats . Res. Commun. Chem. Pathol. Pharmacol. , 9 , 523 – 534 ( 1974. ). [PubMed] [Google Scholar]
  • 28).Ishii , Y. , Fujii , Y. and Homma , M.Gastric acid stimulating action of cysteamine in the rat . Eur. J. Pharmacol. , 36 , 331 – 336 ( 1976. ). [DOI] [PubMed] [Google Scholar]
  • 29).Kirkegaard , P. , Poulsen , S. S. , Loud , F. B. , Halse , C. and Christiansen , J.Cysteamine‐induced duodenal ulcer and acid secretion in the rat . Scand. J. Gastroenterol. , 15 , 621 – 624 ( 1980. ). [DOI] [PubMed] [Google Scholar]
  • 30).Nakahara , K.Special features of intestinal metaplasia and relation to early gastric carcinoma in man; observation by a method in which leucine aminopeptidase activity is used . J. Natl. Cancer Inst. , 61 , 693 – 702 ( 1978. ). [PubMed] [Google Scholar]
  • 31).Johnson , L. R. and Overholt , B. F.Release of histamine into gastric venous blood following injury by acetic or salicylic acid . Gastroenterology , 52 , 505 – 509 ( 1967. ). [PubMed] [Google Scholar]
  • 32).Konturek , S. I. , Brzozowski , T. , Piastucki , I. , Dembinski , A. and Radecki , T.Role of mucosal prostaglandin and DNA synthesis in gastric cytoprotection by luminal epidermal growth factor . Gut , 22 , 927 – 932 ( 1981. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33).Konturek , S. I.Effect of epidermal growth factor on gastrointestinal secretion . Am. Physiol. Soc. , 580 , 246 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 34).Imai , S. , Itoh , M. , Katsumi , K. , Yakoyama , Y. , Miyamoto , T. , Joh , T. , Ikeda , K. , Matsusako , K. , Noguchi , Y. , Tomomatsu , T. , Yasue , K. and Takeuchi , T.Effects of endogenous epidermal growth factor (EGF) on acid secretion, intramucosal mucus and HC1‐induced mucosal injury in the stomach in submandibular gland removed rats . Jpn. Gastroenterol. J. , 84 , 1573 – 1578 ( 1987. ) ( in Japanese ). [PubMed] [Google Scholar]
  • 35).Bayliss , W. M. and Starling , E. H.The mechanism of pancreatic secretion . Physiology , 28 , 325 – 353 ( 1902. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36).Watanabe , H. , Okamoto , T. , Matsuda , M. and Ito , A.Effects of Selbex on X‐ray induced intestinal metaplasia in rats . Basic Clin. , 27 , 481 – 484 ( 1993. ) ( in Japanese ). [Google Scholar]
  • 37).Teglbjaerg , P. S. and Nielsen , H. O.“Small intestinal type” and “colonic type” intestinal metaplasia of the human stomach, and their relationship to the histogenic types of gastric adenocarcinoma . Acta Pathol. Microbiol. Scand. , 86 , 351 – 355 ( 1978. ). [DOI] [PubMed] [Google Scholar]

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