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. 1997 Oct;88(10):934–940. doi: 10.1111/j.1349-7006.1997.tb00311.x

Induction of Aberrant Crypt Foci and Flat‐type Adenocarcinoma in the Colons of Dogs by N‐Ethyl‐N'‐nitro‐N‐nitrosoguanidine and Their Sequential Changes

Kenji Sugiyama 1,✉, Yasushi Oda 2, Kazuhiko Otori 3, Shigeharu Kato 2, Takahiro Hasebe 4, Takahiro Fujii 2, Hisao Tajiri 2, Hiroyasu Esumi 1
PMCID: PMC5921272  PMID: 9414653

Abstract

Sequential endoscopic observation of dog colons was performed during colon carcinogenesis. Two beagle dogs were given suppositories containing N‐ethyl‐N'‐nitro‐N‐nitrosoguanidine (ENNG) every day for five months. In month 3, aberrant crypt foci (ACF), a putative preneoplastic lesion, were found in the colons of both dogs, but not in an untreated dog. The frequency of ACF increased until month 10, and then decreased. In month 9, very small lesions, less than 1 mm in diameter, which were similar to human early flat tumors, were first noticed. One of these lesions grew to about 7 mm in size without a change in its shape for 10 months. There were more than ten flat‐type tumors in the two dogs, but such lesions were not found in the untreated dog. By biopsy, two of the lesions were proved to be well‐differentiated adenocarcinomas histologically. Four polypoid lesions were found in one of the carcinogen‐treated dogs. Thus, flat‐type adenocarcinomas were induced in the dog colon by ENNG, and their development was followed by magnifying endoscopy.

Keywords: Aberrant crypt foci, Flat‐type adenocarcinoma, Dog, Colon carcinogenesis, Endoscopy

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REFERENCES

  • 1. ) Morson , B.The polyp‐cancer sequence in the large bowel . Proc. R. Soc. Med. , 67 , 451 – 457 ( 1974. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. ) Vogelstein , B. , Feason , E. R. , Hamilton , S. R. , Kern , S. E. , Peisinger , A. C. , Leppert , M. , Nakamura , Y. , White , R. , Smits , A. M. M. and Bos , J. L.Genetic alterations during colorectal‐turnor development . N. Engl. J. Med , 319 , 525 – 532 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Aaltonen , L. A. , Peltomäki , P. , Leach , F. S. , Sistonen , P. , Pylkkänen , L. , Mecklin , J.‐P. , Järvinen , H. , Powell , S. M. , Jen , J. , Hamilton , S. R. , Petersen , G. M. , Kinzler , K. W. , Vogelstein , B. and Chapelle , A.Clues to the pathogenesis of familial colorectal cancer . Science , 260 , 812 – 816 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Thibodeau , S. N. , Bren , G. and Schaid , D.Microsatellite instability in cancer of the proximal colon . Science , 260 , 816 – 819 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 5. ) Kariya , A. , Beppu , Y. , Mizuno , K. , Takaki , M. , Mayama , S. , Tazuwa , H. , Ohmori , Y. , Fujita , M. and Nishizawa , M.A case of early colonic cancer type He associated with familial polyposis coli . Stomach Intest. 12 , 1359 – 1364 ( 1977. ) ( in Japanese with English abstract ). [Google Scholar]
  • 6. ) Kudo , S. , Kusaka , H. , Kimata , H. , Fujii , T. and Himori , M.The diagnosis and treatment of colorectal sm cancer . Stomach Intest. , 26 , 764 – 775 ( 1991. ) ( in Japanese with English abstract ). [Google Scholar]
  • 7. ) Minamoto , T. , Sawaguchi , K. , Mai , M. , Yamashita , N. , Sugimura , T. and Esumi , H.Infrequent K‐ras activation in superficial‐type (flat) colorectal adenomas and adenocarcinomas . Cancer Res. , 54 , 2841 – 2844 ( 1994. ). [PubMed] [Google Scholar]
  • 8. ) Mueller , J. , Mueller , E. , Hoepner , I. , Jutting , J. , Bethke , B. , Stolte , M. and Höfler , H.Expression of bcl‐2 and p53 in de novo and ex‐adenoma colon carcinoma: a comparative immunohistochemical study . J. Pathol. , 180 , 259 – 265 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Kuramoto , T. and Oohara , T.Flat early cancers of the large intestine . Cancer , 64 , 950 – 955 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 10. ) Iishi , H. , Tatsuta , M. , Tsutsui , S. , Imanishi , K. , Otani , T. , Okuda , T. , Ishiguro , S. and Taniguchi , H.Early depressed adenocarcinomas of the large intestine . Cancer , 69 , 2406 – 2410 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Minamoto , T. , Sawaguchi , K. , Ohta , T. , Itoh , T. and Mai , M.Superficial‐type adenomas and adenocarcinomas of the colon and rectum: a comparative morphological study , Gastroenterology , 106 , 1436 – 1443 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 12. ) Jen , J. , Powell , S. M. , Papadopoulos , N. , Smith , K. J. , Hamilton , S. R. , Vogelstein , B. and Kinzler , K. W.Molecular determinants of dysplasia in colorectal lesions . Cancer Res. , 54 , 5523 – 5526 ( 1994. ). [PubMed] [Google Scholar]
  • 13. ) Konstantakos , A. K. , Siu , I. , Pretlow , T. G. , Stellato , T. A. and Pretlow , T. P.Human aberrant crypt foci with carcinoma in situ from a patient with sporadic colon cancer . Gastroenterology , 111 , 772 – 777 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Heinen , C. D. , Shivapukar , N. , Tang , Z. , Groden , J. and Alabaster , OMicrosatellite instability in aberrant crypt foci from human colons . Cancer Res. , 56 , 5339 – 5341 ( 1996. ). [PubMed] [Google Scholar]
  • 15. ) Bird , R. P.Observation and quantification of aberrant crypts in the murine colon treated with a colon carcinogen . Cancer Lett. , 37 , 149 – 151 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 16. ) Stopera , S. , Murphy , L. and Bird , R. P.Evidence for ras gene mutation in azoxymethane‐induced colonic aberrant crypts in Sprague‐Dawley rats: earliest recognizable precursor lesion of experimental colon cancer . Carcinogenesis , 13 , 2081 – 2085 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 17. ) Pretlow , T. P. , Barrow , B. J. , Ashton , W. S. , O'Riordan , M. A. , Pletlow , T. G. , Jureisek , J. A. and Satellato , T. A.Aberrant crypts :putative preneoplastic foci in human colonic mucosa . Cancer Res. , 51 , 564 – 567 ( 1991. ). [PubMed] [Google Scholar]
  • 18. ) Roncucci , L. , Stamp , D. , Medline , A. , Cullen , J. and Bruce , W.Identification and quantification of aberrant crypt foci and mieroadenomas in the human colon . Hum. Pathol , 22 , 287 – 294 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 19. ) Otori , K. , Sugiyama , K. , Hasebe , T. , Fukushima , S. and Esumi , H.Emergence of adenomatous aberrant crypt foci (ACF) from hyperplastic ACF with concomitant increase in cell proliferation . Cancer Res. , 55 , 4743 – 4746 ( 1995. ). [PubMed] [Google Scholar]
  • 20. ) Kamano , T. , Kishino , H. , Mizukami , K. , Azuma , N. , Tamura , J. , Katami , A. and Kidokoro , T.Histopathological study on N‐ethyl‐N'‐nitro‐N‐nitrosoguanidine‐induced colon cancer in dogs . Int. J. Cancer , 32 , 255 – 258 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Kudo , S. , Miura , K. , Takano , Y. and Ban‐nai , H.Detection of colorectal cancer . Stomach Intest. , 25 , 801 – 812 ( 1990. ) ( in Japanese with English abstract ). [Google Scholar]
  • 22. ) Hunt , D. R. and Cherian , M.Endoscopic diagnosis of small flat carcinoma of the colon. Report of three cases . Dis. Colon Rectum , 33 , 143 – 147 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Jaramillo , E. , Watanabe , M. , Slezak , P. and Rubio , C.Flat neoplastic lesions of the colon and rectum detected by high‐resolution video endoscopy and chronoscopy . Gastrointest. Endosc. , 42 , 114 – 122 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 24. ) Stolte , M. and Bothke , B.Colorectal mini‐de novo carcinoma: a reality in Germany too . Endoscopy , 27 , 286 – 290 ( 1995. ). [DOI] [PubMed] [Google Scholar]
  • 25. ) Owen , D. A.Flat adenoma, flat carcinoma, and de novo carcinoma of the colon . Cancer , 77 , 3 – 6 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 26. ) Rubio , C. and Shetye , J.Flat adenoma‐adenocarcinoma sequence in the colon of rats . Dis. Colon Rectum , 37 , 1300 – 1306 ( 1994. ). [DOI] [PubMed] [Google Scholar]

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