Skip to main content
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1993 Dec;84(12):1258–1264. doi: 10.1111/j.1349-7006.1993.tb02831.x

Induction of Glandular Stomach Cancers in C3H Mice Treated with N‐Methyl‐N‐nitrosourea in the Drinking Water

Masae Tatematsu 1, Masami Yamamoto 1, Hitoshi Iwata 1, Hiroko Fukami 1, Hirofumi Yuasa 1, Noriaki Tezuka 1, Tsuneo Masui 1, Hayao Nakanishi 1
PMCID: PMC5919110  PMID: 8294216

Abstract

Establishment of an animal model of stomach carcinogenesis in mice was attempted using N‐methyl‐N‐nitrosourea (MNU) in the drinking water. One hundred and forty‐eight male 6‐week‐old C3H mice were given MNU in their drinking water at a concentration of 120 ppm (group 1), 60 ppm (group 2), 30 ppm (group 3) or 0 ppm (group 4) for 30 weeks. At the end of this time, dose‐related induction of adenomatous hyperplasias was found. From weeks 31 to 54 adenocarcinomas developed in a dose‐dependent manner in groups 1, 2 and 3. In total, 6 well differentiated and 5 poorly differentiated adenocarcinomas as well as 6 signet ring cell carcinomas arose in 15 stomach cancer‐bearing animals in group 1, 4 well differentiated and 2 poorly differentiated adenocarcinomas with one signet ring cell carcinoma in 5 mice of group 2 and one well differentiated adenocarcinoma in group 3. In the forestomach, only one squamous cell carcinoma was found at week 54 in group 1 along with a single well differentiated adenocarcinoma in the duodenum. Thus, MNU in the drinking water selectively induced neoplastic lesions in the glandular stomach epithelium of mice.

Keywords: N‐Methyl‐N‐nitrosourea, Glandular stomach cancer, Mouse, Dose response

Full Text

The Full Text of this article is available as a PDF (591.6 KB).

REFERENCES

  • 1).Mori , K.Carcinoma of the glandular stomach of mice by instillation of 4‐nitroquinoline 1‐oxide . Gann , 58 , 389 – 393 ( 1967. ). [PubMed] [Google Scholar]
  • 2).Mori , K. , Ohta , A. , Murakami , T. , Tamura , M. and Kondo , M.Carcinoma of the glandular stomach of mice induced by 4‐hydroxyaminoquinoline 1‐oxide hydrochloride . Gann , 60 , 151 – 154 ( 1969. ). [PubMed] [Google Scholar]
  • 3).Sugimura , T. and Kawachi , T.Experimental stomach cancer . Methods Cancer Res. , 7 , 245 – 308 ( 1973. ). [Google Scholar]
  • 4).Hirose , M. , Fukushima , S. , Tanaka , H. , Asakawa , E. , Takahashi , S. and Ito , N.Carcinogenicity of catechol in F344 rats and B6C3F1 mice . Carcinogenesis , 14 , 525 – 529 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 5).Watanabe , H. , Ogundigie , P. O. , Takahashi , T. , Ishimoto , T. and Ito , A.Induction of signet ring cell carcinomas in X‐irradiated hypocatalasemic mice (C3H/Cbs) . Jpn. J. Cancer Res. , 82 , 1175 – 1177 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6).Tatematsu , M. , Ogawa , K. , Hoshiya , T. , Shichino , Y. , Kato , T. , Imaida , K. and Ito , N.Induction of adenocarcinomas in the glandular stomach of BALB/c mice treated with N‐methyl‐N‐nitrosourea . Jpn. J. Cancer Res. , 83 , 915 – 918 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7).Hirono , I. and Shibuya , C.Induction of stomach cancer by a single dose of N‐methyl‐N'‐nitro‐N‐nitrosoguanidine through a stomach tube . In “ Topics in Chemical Carcinogenesis ,” ed. Nakahara W. , Takayama S. , Sugimura T. , and Odashima S. , pp . 121 – 131 ( 1972. ). University of Tokyo Press; , Tokyo . [Google Scholar]
  • 8).Shirai , T. , Imaida , K. , Fukushima , S. , Hasegawa , R. , Tatematsu , M. and Ito , N.Effects of NaCl, Tween 60 and a low dose of N‐ethyl‐N'‐nitro‐N‐nitrosoguanidine on gastric carcinogenesis of rats give a single dose of N‐methyl‐N'‐nitro‐N‐nitrosoguanidine . Carcinogenesis , 3 , 1419 – 1422 ( 1982. ). [DOI] [PubMed] [Google Scholar]
  • 9).Sugimura , T. and Fujimura , S.Tumor production in glandular stomach of rat by N‐methyl‐N'‐nitro‐N‐nitrosoguanidine . Nature , 216 , 943 – 944 ( 1967. ). [DOI] [PubMed] [Google Scholar]
  • 10).Takahashi , M. , Shirai , T. , Fukushima , S. , Hananouchi , M. , Hirose , M. and Ito , N.Effect of fundic ulcers induced by iodoacetamide on development of gastric tumors in rats treated with N‐methyl‐N'‐nitro‐N‐nitrosoguanidine . Gann , 67 , 47 – 54 ( 1976. ). [PubMed] [Google Scholar]
  • 11).Tatematsu , M. , Katsuyama , T. , Fukushima , S. , Takahashi , M. , Shirai , T. , Ito , N. and Nasu , T.Mucin histochemistry by paradoxical concanavalin A staining in experimental gastric cancers induced in Wistar rats by N‐methyl‐N'‐nitro‐N‐nitrosoguanidine or 4‐nitroquinoline 1‐oxide . J. Natl. Cancer Inst. , 64 , 835 – 843 ( 1980. ). [PubMed] [Google Scholar]
  • 12).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]
  • 13).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]
  • 14).Saito , T. , Inokuchi , K. , Takayama , S. and Sugimura , T.Sequential morphological changes in N‐methyl‐N'‐nitro‐N‐nitrosoguanidine carcinogenesis in the glandular stomach of rats . J. Natl. Cancer Inst. , 44 , 769 – 783 ( 1970. ). [PubMed] [Google Scholar]
  • 15).Hirota , N. , Aonuma , T. , Yamada , S. , Kawai , T. , Saito , K. and Yokoyama , T.Selective induction of glandular stomach carcinoma in F344 rats by N‐methyl‐N‐nitrosourea . Jpn. J. Cancer Res. , 78 , 634 – 638 ( 1987. ). [PubMed] [Google Scholar]
  • 16).Takahashi , M. , Fukushima , S. and Sato , H.Carcinogenic effect of N‐methyl‐N'‐nitro‐N‐nitrosoguanidine with various kinds of surfactant in the glandular stomach of rats . Gann , 64 , 211 – 218 ( 1973. ). [PubMed] [Google Scholar]
  • 17).Tatematsu , M. , Takahashi , M. , Fukushima , S. , Hananouchi , M. and Shirai , T.Effects in rats of sodium chloride on experimental gastric cancers induced by N‐methyl‐N'‐nitro‐N‐nitrosoguanidine or 4‐nitroquinoline‐1‐oxide . J. Natl. Cancer Inst. , 55 , 101 – 106 ( 1975. ). [DOI] [PubMed] [Google Scholar]
  • 18).Tahara , E. and Haizuka , S.Effect of gastro‐enteropancreatic endocrine hormones on the histogenesis of gastric cancer in rats induced by N‐methyl‐N'‐nitro‐N‐nitrosoguanidine; with special reference to development of scirrhous gastric cancer . Gann , 66 , 421 – 426 ( 1975. ). [PubMed] [Google Scholar]
  • 19).Hare , W. V. , Stewart , H. L. , Bennett , J. G. and Lorenz , E.Tumors of the glandular stomach induced in rats by intramural injection of 20‐methylcholanthrene . J. Natl. Cancer Inst. , 12 , 1019 – 1055 ( 1952. ). [PubMed] [Google Scholar]
  • 20).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]
  • 21).Lauren , P.The two histological main types of gastric carcinoma: diffuse and so‐called intestinal‐type carcinoma. An attempt at a histoclinical classification . Acta Pathol. Microbiol. Scand. , 64 , 31 – 49 ( 1965. ). [DOI] [PubMed] [Google Scholar]
  • 22).Ming , S. C. , Goldman , H. and Freima , D. G.Intestinal metaplasia and histogenesis of carcinoma in human stomach. Light and electron microscopic study . Cancer , 20 , 1418 – 1429 ( 1967. ). [DOI] [PubMed] [Google Scholar]
  • 23).Tatematsu , M. , Ichinose , M. , Miki , K. , Hasegawa , R. , Kato , T. and Ito , N.Gastric and intestinal phenotypic expression of human stomach cancers as revealed by pepsinogen immunohistochemistry and mucin histochemistry . Acta Pathol. Jpn. , 40 , 494 – 504 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 24).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]
  • 25).Tatematsu , M. , Katsuyama , T. , Furihata , C. , Tsuda , H. and Ito , N.Stable intestinal phenotypic expression of gastric and small intestinal tumor cells induced by N‐methyl‐N'‐nitro‐N‐nitrosoguanidine or methylnitrosourea in rats . Gann , 75 , 957 – 965 ( 1984. ). [PubMed] [Google Scholar]

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

RESOURCES