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Table of Contents
Vol. 31, No. 3, 1999
Issue release date: May–June 1999
Eur Surg Res 1999;31:272–280
(DOI:10.1159/000008703)

Azoxymethane-Induced Aberrant Crypt Foci and Colorectal Tumors in F344 Rats: Sequential Analysis of Growth

Ghirardi M. · Nascimbeni R. · Villanacci V. · Fontana M.G. · Di Betta E. · Salerni B.
Departments of aSurgery and bPathology, University of Brescia, Italy

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Abstract

Previous studies are consistent with the hypothesis that aberrant crypt foci (ACF) could be intermediate biomarkers in colorectal carcinogenesis. The present controlled experimental trial was performed to sequentially analyze ACF progression in rat colonic mucosa. F344 rats were administered 2-weekly doses of azoxymethane (15 mg/kg body weight, s.c.) and sacrificed 6, 12, 20, 30 and 36 weeks after the first carcinogen injection. Control groups of untreated rats were sacrificed at the same time points. The number of ACF per area, their multiplicity (number of crypts per focus), ACF frequency and multiplicity according to each colonic site, histology of ACF and macroscopic lesions were recorded. No ACF were found in control animals. In treated animals, the number of ACF per area and the multiplicity progressively and significantly increased throughout the study. ACF were prevalent in the mid colon. Lower frequencies were registered in the distal colon and rectum. ACF were rare in the proximal colon and cecum. By histology, ACF presented superficial and extensive hyperplasia. Tumors were found in the 30th and 36th week. Adenomas and well-differentiated adenocarcinomas were in the distal colon. All proximal neoplasms were signet ring cell carcinomas. In our study, ACF growing features and distribution are not correlated to adenoma and adenocarcinoma distribution. It is conceivable that signet ring cell carcinomas arising in the proximal colon, where ACF are rare, could present a different pathway of growth. The preneoplastic role of ACF and their function as intermediate biomarkers in colorectal carcinogenesis remain to be clarified.



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References

  1. McLellan EA, Bird RP: Aberrant crypts: Potential preneoplastic lesions in the murine colon. Cancer Res 1988;48:6187–6192.
  2. McLellan EA, Medline A, Bird RP: Dose response and proliferative characteristics of aberrant crypt foci: Putative preneoplastic lesions in rat colon. Carcinogenesis 1991;12:2093–2098.

    External Resources

  3. McLellan EA, Medline A, Bird RP: Sequential analyses of the growth and morphological characteristics of aberrant crypt foci: Putative preneoplastic lesions. Cancer Res 1991;51:5270–5274.
  4. Stopera SA, Bird RP: Expression of ras oncogene mRNA and protein in aberrant crypt foci. Carcinogenesis 1992;13:1863–1868.
  5. Stopera SA, Davie JR, Bird RP: Colonic aberrant crypt foci are associated with increased expression of c-fos: The possible role of modified c-fos expression in preneoplastic lesions in colon cancer. Carcinogenesis 1992;13:573–578.

    External Resources

  6. Reddy BS, Chinthalapally VR, Rivenson A, Kelloff G: Inhibitory effect of aspirin on azoxymethane-induced colon carcinogenesis in F344 rats. Carcinogenesis 1993;14:1493–1497.
  7. Pereira MA, Barnes LH, Rassman VL, Kelloff GV, Steele VE: Use of azoxymethane-induced foci of aberrant crypts in rat colon to identify potential cancer chemopreventive agents. Carcinogenesis 1994;15:1049–1054.

    External Resources

  8. Pereira MA, Barnes LH, Steele VE, Kelloff GV, Lubet RA: Piroxicam-induced regression of azoxymethane-induced aberrant crypt foci and prevention of colon cancer in rats. Carcinogenesis 1996;17:373–376.

    External Resources

  9. Carter JW, Lancaster HK, Hardmann WE, Cameron IL: Distribution of intestine-associated lymphoid tissue, aberrant crypt foci, and tumors in the large bowel of 1,2-dimethylhydrazine-treated mice. Cancer Res 1994;54:4304–4307.

    External Resources

  10. Hardmann WE, Cameron IL, Heitman DW, 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 1991;51:6388–6392.

    External Resources

  11. Cameron IL, Garza J, Hardmann WE: Distribution of lymphoid nodules, aberrant crypt foci and tumors in the colon of carcinogen-treated rats. Br J Cancer 1996;73:893–898.

    External Resources

  12. Park HS, Goodlad RA, Wright NA: The incidence of aberrant crypt foci and colonic carcinoma in dimethylhydrazine-treated rats varies in a site-specific manner and depends on tumor histology. Cancer Res 1997;57:4507–4510.

    External Resources

  13. Barrow BJ, O’Riordan MA, Stellato TA, Calkins BM, Pretlow TP: Enzyme-altered foci in colons of carcinogen-treated rats. Cancer Res 1990;50:1911–1916.

    External Resources

  14. Bird PR: Observation and quantification of aberrant crypts in the murine colon treated with a colon carcinogen: Preliminary findings. Cancer Lett 1987;37:147–151.
  15. Morson BC, Dawson IMP: Benign epithelial tumours and polyps; in Morson BC, Dawson IMP (eds): Gastrointestinal Pathology. Oxford, Blackwell Scientific, 1990, pp 563–596.
  16. Nascimbeni R, Villanacci V, Donato F, Salerni B: Hyperplastic/dysplastic pathways in aberrant crypt foci from human colon. Gastroenterology 1998;114:G2691.
  17. Glanz SA: The specific case of two groups: The t test; in Glanz SA (ed): Primer of Bio-Statistics, ed 4. New York, McGraw-Hill, 1992, pp 88–91.
  18. Bird RP: Role of aberrant crypt foci in understanding the pathogenesis of colon cancer. Cancer Lett 1995;93:55–71.
  19. Shpitz B, Hay K, Medline A, Bruce RW, Bull SB, Gallinger S, Stern H: Natural history of aberrant crypt foci. A surgical approach. Dis Colon Rectum 1996;39:763–767.

    External Resources



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