Skip to main content
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1993 May;84(5):495–500. doi: 10.1111/j.1349-7006.1993.tb00166.x

Effect of Experimental Hypochlorhydria on the Histological Differentiation of Adenocarcinomas in the Canine Stomach

Takeshi Sano 1,, Oichiro Kobori 1, Sho Kuroki 1, Hirokazu Nagawa 1, Tetsuichiro Muto 1
PMCID: PMC5919171  PMID: 8320166

Abstract

Hypochlorhydria is considered to be a risk factor for gastric cancer, both clinically and experimentally. In humans, the hypo‐acidic condition appears to be closely associated with the development of differentiated‐tyne gastric carcinomas. We investigated relationships between antral pH and histological types of gastric cancer using an animal model. A total of 7.65 g of N‐ethyl‐N′‐nitro‐N‐nitrosoguanidine (ENNG) was orally administered to male beagle dogs. Subsequently, the dogs were divided into four groups and underwent four surgical interventions designed to create various conditions in the antrum. Antral pM was recorded at the time of killing after an observation period ranging from 16 to 33 months. The number of gastrin‐secreting cells (G‐cells) was counted after immunohistochemical staining. Carcinomas were found in the antrum of 12 of the 21 dogs that had survived. Although limited doses of ENNG, such as those used in this study, have been reported to produce only undifferentiated adenocarcinomas, differentiated adenocarcinomas were found in seven of these 12 dogs. Antral pH and the number of G‐cells were significantly higher in these seven dogs than in the other five dogs, which had developed only undifferentiated adenocarcinomas. Bile inflow showed no significant effect on the development of differentiated adenocarcinomas. Neither atrophic gastritis nor intestinal metaplasia was seen in any of the dogs. These results suggest that the hypo‐acidic condition itself may play a role in the development of differentiated adenocarcinomas.

Keywords: Gastric cancer, Carcinogenesis, Acid, Histological differentiation

Full Text

The Full Text of this article is available as a PDF (535.4 KB).

REFERENCES

  • 1. ) Tatsuta , M. , Yamamura , H. , Iishi , H. , Ichii , M. , Noguchi , S. , Baba , M. and Taniguchi , H.Promotion by vagotomy of gastric carcinogenesis induced by N‐methyl‐N'‐nitro‐N‐nitrosoguanidine in Wistar rats . Cancer Res. , 45 , 194 – 197 ( 1985. ). [PubMed] [Google Scholar]
  • 2. ) Deveney , C. W. , Freeman , H. and Way , L. W.Experimental gastric carcinogenesis in the rat: effects of hypergastrinemia and acid secretion . Am. J. Surg. , 139 , 49 – 54 ( 1980. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Kurihara , M. , Shirakabe , H. , Murakami , T. , Yasui , A. , Izumi , T. , Sumida , M. and Igarashi , A.A new method for producing adenocarcinomas in the stomach of dogs with N‐ethyl‐N'‐nitro‐N‐nitrosoguanidine . Gann , 65 , 163 – 177 ( 1974. ). [PubMed] [Google Scholar]
  • 4. ) Sunagawa , M. , Takeshita , K. , Nakajima , A. , Ochi , K. , Habu , H. and Endo , M.Duration of ENNG administration and its effect on histological differentiation of experimental gastric cancer . Br. J. Cancer , 52 , 771 – 779 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5. ) Kobori , O. , Vuillot , M. T. and Martin , F.Growth responses of rat stomach cancer cells to gastro‐enteropancreatic hormones . Int. J. Cancer , 30 , 65 – 67 ( 1982. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Watson , S. , Durrant , L. and Morris , D.Gastrin: growth enhancing effects on human gastric and colonic tumour cells . Br. J. Cancer , 59 , 554 – 558 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. ) Salmon , R. J. , Laurent , M. and Thierry , J. P.Effect of taurocholic acid feeding on methyl‐nitro‐N‐nitrosoguanidine induced gastric tumors . Cancer Lett , 22 , 315 – 320 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Kobori , O. , Shimizu , T. , Maeda , M. , Atomi , Y. , Watanabe , J. , Shoji , M. and Morioka , Y.Enhancing effect of bile and bile acid on stomach tumorigenesis induced by N‐methyl‐N'‐nitro‐N‐nitrosoguanidine in Wistar rats . J. Natl. Cancer Inst. , 73 , 853 – 861 ( 1984. ). [PubMed] [Google Scholar]
  • 9. ) Kurihara , M. , Shirakabe , H. , Yamaya , F. , Miyazaki , K. , Maruyama , T. , Izumi , T. , Yasui , A , and Kamano , T.Gastric carcinoma in dogs produced by the combined use of N‐ethyl‐N'‐nitro‐N‐nitrosoguanidine (ENNG) and gastrin . Acta Pathol Jpn. , 29 , 171 – 176 ( 1979. ). [DOI] [PubMed] [Google Scholar]
  • 10. ) Tatsuta , M. , Itoh , T. , Okuda , S. , Wada , A. , Taniguchi , H. , Tamura , H. and Yamamura , H.Effects of gastrin and histamine on gastric carcinogenesis induced in rats by N‐methyl‐N'‐nitro‐N‐nitrosoguanidine . Eur. J. Cancer , 16 , 631 – 638 ( 1980. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Tani , N. , Harasawa , S. , Suzuki , S. , Miwa , M. , Nomiyama , T. , Senoue , I. , Kikuchi , K. , Makino , T. , Shibata , H. and Miwa , T.Gastric acid secretion and plasma gastrin response to test meal in patients with gastric cancer . Tokai J. Exp. Clin. Med. , 1 , 169 – 172 ( 1982. ). [PubMed] [Google Scholar]
  • 12. ) Morson , B. C. , Sobin , L. H. , Grundmann , E. , Johansen , A. , Nagayo , T. and Serck‐Hanssen , A.Precancerous conditions and epithelial dysplasia in the stomach . J. Clin. Pathol. , 33 , 711 – 721 ( 1980. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. ) Correa , P.Precursors of gastric and esophageal cancer . Cancer , 50 , 2554 – 2565 ( 1982. ). [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES