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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1996 Dec;87(12):1199–1203. doi: 10.1111/j.1349-7006.1996.tb03133.x

Development of Aberrant Crypt Foci Involves a Fission Mechanism as Revealed by Isolation of Aberrant Crypts

Yasunobu Fujimitsu 1,2, Hayao Nakanishi 1, Ken‐ichi Inada 1, Takasuke Yamachika 1, Masutaro Ichinose 1, Hiroko Fukami 1, Masae Tatematsu 1,
PMCID: PMC5921030  PMID: 9045953

Abstract

Morphological analysis of isolated colonic crypts in rats, postnatally, indicated that the crypts reproduce themselves by a fission mechanism, the division beginning at the crypt base and proceeding upwards until there are two separate crypts. Occasionally, before the separation is complete, a second fission process starts on one or both sides of a bifurcating crypt and a triple‐branched or quadruple‐branched crypt results. Analysis of isolated aberrant crypt foci (ACF) in rats treated with 1,2‐dimethylhydrazine revealed that the development of ACF consisting of multiple crypts is also due to a fission mechanism. Initially, an indentation appears at the base of a single ACF crypt, with subsequent formation of a bifurcation and eventual crypt division.

Keywords: Aberrant crypt foci, Fission mechanism, Crypt isolation technique

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REFERENCES

  • 1. ) Bird , R. P.Observation and quantification of aberrant crypts in the murine colon treated with a colon carcinogen: preliminary findings . Cancer Lett. , 37 , 147 – 151 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 2. ) McLellan , E. A. and Bird , R. P.Aberrant crypts: potential preneoplastic lesions in the murine colon . Cancer Res. , 48 , 6187 – 6192 ( 1988. ). [PubMed] [Google Scholar]
  • 3. ) McLellan , E. A. , Medline , A. and Bird , R. P.Dose response and proliferative characteristics of aberrant crypt foci: putative preneoplastic lesions in rat colon . Carcinogenesis , 12 , 2093 – 2098 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Pretlow , T. P. , Barrow , B. J. , Ashton , W. S. , O'Riordan , M. A. , Pretlow , T. G. , Jurcisek , J. A. and Stellato , T. A.Aberrant crypts: putative preneoplastic foci in human colonic mucosa . Cancer Res. , 51 , 1564 – 1567 ( 1991. ). [PubMed] [Google Scholar]
  • 5. ) Roncucci , L. , Stamp , D. , Medline , A. , Cullen , J. B. and Bruce , W. R.Identification and quantification of aberrant crypt foci and microadenomas in the human colon . Hum. Pathol. , 22 , 287 – 294 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 6. ) Pretlow , T. P. , O'Riordan , M. A. , Pretlow , T. G. and Stellato , T. A.Aberrant crypts in human colonic mucosa: putative preneoplastic lesions . J. Cell. Biochem. , 16 ( Suppl. G ), 55 – 62 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 7. ) Pretlow , T. P. , O'Riordan , M. A. , Kolman , M. F. and Jurcisek , J. A.Colonic aberrant crypts in azoxymethane‐treated F344 rats have decreased hexosaminidase activity . Am. J. Pathol. , 136 , 13 – 16 ( 1990. ). [PMC free article] [PubMed] [Google Scholar]
  • 8. ) Stopera , S. A. and Bird , R. P.Expression of ras oncogene mRNA and protein in aberrant crypt foci . Carcinogenesis , 13 , 1863 – 1868 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Stopera , S. A. , Murphy , L. C. and Bird , R. P.Evidence for a ras gene mutation in azoxymethane‐induced colonic aberrant crypts in Sprague‐Dawley rats: earliest recognizable precursor lesions of experimental colon cancer . Carcinogenesis , 13 , 2081 – 2085 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 10. ) Vivona , A. A. , Shpitz , B. , Medline , A. , Bruce , W. R. , Hay , K. , Ward , M. A. , Stern , H. S. and Gallinger , S.K‐ras mutations in aberrant crypt foci, adenomas and adenocarcinomas during azoxymethane‐induced colon carcinogenesis . Carcinogenesis , 14 , 1777 – 1781 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) McLellan , E. A. , Medline , A. and Bird , R. P.Sequential analyses of the growth and morphological characteristics of aberrant crypt foci: putative preneoplastic lesions . Cancer Res. , 51 , 5270 – 5274 ( 1991. ). [PubMed] [Google Scholar]
  • 12. ) Maskens , A. P.Histogenesis of colon glands during post‐natal growth . Acta Anat. , 100 , 17 – 26 ( 1978. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Maskens , A. P. and Dujardin , L. R.Kinetics of tissue proliferation in colorectal mucosa during post‐natal growth . Cell Tissue Kinet. , 14 , 467 – 477 ( 1981. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Bjerknes , M. and Cheng , H.Methods for the isolation of intact epithelium from the mouse intestine . Anat. Rec. , 199 , 565 – 574 ( 1981. ). [DOI] [PubMed] [Google Scholar]
  • 15. ) Yamashita , N. , Minamoto , T. , Onda , M. , Esumi , H.Increased cell proliferation of azoxymethane‐induced aberrant crypt foci of rat colon . Jpn. J. Cancer Res. , 85 , 692 – 698 ( 1994. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16. ) Griffiths , D. F. , Davies , S. J. , Williams , D. , Williams , G. T. and Williams , E. D.Demonstration of somatic mutation and colonic crypt clonality by X‐linked enzyme histochemistry . Nature , 333 , 461 – 463 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 17. ) Tatematsu , M. , Masui , T. , Fukami , H. , Yamamoto , M. , Nakanishi , H. , Inada , K. , Kusakabe , M. and Sakakura , T.Primary monoclonal and secondary polyclonal growth of colon neoplastic lesions in C3H/HeNBALB/c chimeric mice treated with 1,2‐dimethylhydrazine: immunohistochemical detection of C3H strain‐specific antigen and simple sequence length polymorphism analysis of DNA . Int. J. Cancer , 66 , 234 – 238 ( 1996. ). [DOI] [PubMed] [Google Scholar]
  • 18. ) Tudek , B. , Bird , R. P. and Bruce , W. R.Foci of aberrant crypts in the colons of mice and rats exposed to carcinogens associated with foods . Cancer Res. , 49 , 1236 – 1240 ( 1989. ). [PubMed] [Google Scholar]
  • 19. ) Hardman , W. E. , Cameron , I. L. , Heitman , D. W. and Contreras , E.Demonstration of the need for end point validation of putative biomarkers: failure of aberrant crypt foci to predict colon cancer incidence . Cancer Res. , 51 , 6388 – 6392 ( 1991. ). [PubMed] [Google Scholar]
  • 20. ) Thorup , I. , Meyer , O. and Kristiansen , E.Influence of a dietary fiber on development of dimethylhydrazine‐ induced aberrant crypt foci and colon tumor incidence in Wistar rats . Nutr. Cancer , 21 , 177 – 182 ( 1994. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Tatematsu , M. , Nagamine , Y. and Farber , E.Redifferentiation as a basis for remodeling of carcinogen‐induced hepatocyte nodules to normal appearing liver . Cancer Res. , 43 , 5049 – 5058 ( 1983. ). [PubMed] [Google Scholar]
  • 22. ) Chang , W. W. and Leblond , C. P.Renewal of the epithelium in the descending colon of the mouse. I. Presence of three cell populations: vacuolated‐columnar, mucous and argentaffin . Am. J. Anat. , 131 , 73 – 99 ( 1971. ). [DOI] [PubMed] [Google Scholar]

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