Skip to main content

Advertisement

SpringerLink
Log in

Patchy field defects of apoptosis resistance and dedifferentiation in flat mucosa of colon resections from colon cancer patients

  • Original Articles
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Abnormal areas in normal-appearing falt colonic mucosa (field defects) may predispose individuals to colon cancer. Markers of field defects would indicate cancer risk.

Methods

We evaluated apoptosis capability, dedifferentiation, frequency of simple aberrant crypts, aberrant crypt foci, microadenomas, and total nicotinamide adenine dinucleotide levels at locations with normal-appearing flat mucosa obtained from colon resections.

Results

Among goblet cells from colonic mucosa samples of individuals without colonic neoplasia, there was a high mean deoxycholate-induced apoptotic index (AI) of 59.1% and highDolichos biflorus agglutinin (DBA) lectin reactivity (differntiation) in 85.0% of samples. In contrast, flat mucosa samples from colon cancer patients had a significantly (P<.01) lower average AI of 37.4%, and a significantly (P=.03) lower percentage (40.5%) had high DBA reactivity. For colon cancer patients, AI and DBA reactivity values were patchy within a resection. Nicotinamide adenine dinucleotide levels were highly variable among individuals without neoplasia, and aberrant crypt focia and microadenomas were rare.

Conclusions

AI and aberrant DBA reactivity are promising indicators of colon cancer risk. Our results attest to the importance of obtaining multiple samples to assess colon cancer risk because of the patchy nature of field defects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis.Cell 1990;61:759–67.

    Article  PubMed  CAS  Google Scholar 

  2. Issa J-PJ, Vertino PM, Boehm CD, Newsham IF, Baylin SB. Switch from monoallelic to biallelic humanIGF2 promoter methylation during aging and carcinogenesis.Proc Natl Acad Sci USA 1966;93:11757–62.

    Article  Google Scholar 

  3. Baylin S. Tying it all together: epigenetics, genetics, cell cycle, and cancer.Science 1997;277:1948–9.

    Article  PubMed  CAS  Google Scholar 

  4. Bernstein C, Bernstein H, Payne CM, Garewal H. Field defects in progression to adenocarcinoma of the colon and esophagus.Electronic J Biotechnol (online) 2000;3. Available at: http://www. ejb.org/content/vol3/issue3/full/1/. Accessed December 15, 2000.

  5. Payne CM, Bernstein H, Berntein C, Garewal H. Role of apoptosis in biology and pathology: resistance to apoptosis in colon carcinogenesis.Ultrastruct Pathol 1995;19:221–48.

    PubMed  CAS  Google Scholar 

  6. Garewal H, Bernstein H, Bernstein C, Sampliner R, Payne C. Reduced bile acid-induced apoptosis in “normal” colorectal mucosa: a potential biological marker for cancer risk.Cancer Res 1996;56:1480–3.

    PubMed  CAS  Google Scholar 

  7. Bernsein C, Bernstein H, Garewal H, et al. A bile acid-induced apoptosis assay for colon cancer risk and associated quality control studie.Cancer Res 1999;59:2353–7.

    Google Scholar 

  8. Corbe SW, Clarke AR, Gledhill S, Wyllie AH. P53-dependent and-independent links between DNA-damage, apoptosis and mutation frequency in ES cells.Oncogene 1999;18:1537–44.

    Article  CAS  Google Scholar 

  9. Kuo M-L., Shiah S-G, Wang C-J, Chuang S-E. Suppression of apoptosis by Bcl-2 to enhance benzene metabolites-induced oxidative DNA damage and mutagenesis: a possible mechanism of carcinogenesis.Mol Pharmacol 1999;55:894–901.

    PubMed  CAS  Google Scholar 

  10. Williams GT, Critchlow MR, Hedge VL, O’Hare KB. Molecular failure of apoptosis: inappropriate cell survival and mutagenesis?Toxicol Lett 1998;102–103:485–9.

    Article  PubMed  Google Scholar 

  11. Heerdt BG, Houston MA, Augelicht LH. Potentiation by specific short-chain fatty acids of differentiation and apoptosis in human colonic carcinoma cell lines.Cancer Res 1994;54:3288–94.

    PubMed  CAS  Google Scholar 

  12. Hague A, Manning AM, Hanlon KA, Huschtscha LI, Hart D, Paraskeva C. Sodium butyrate induces apoptosis in human colonic tumour cell lines in a p53-independent pathway: implications for the possille role of dietary fibre in the prevention of large-bowel cancer.Int J Cancer 1993;55:498–505.

    PubMed  CAS  Google Scholar 

  13. Stewart MS, Davis RL, Walsh LP, Pence BC. Induction of differentiation and apoptosis by sodium selenite in human colonic carcinoma cells (HT29).Cancer Lett 1997;117:35–40.

    Article  PubMed  CAS  Google Scholar 

  14. Chang W-CL, Chapkin RS, Lupton JR. Fish oil blocks azoxymethane-induced rat colon tumorigenesis by increasing cell differentiation and apoptosis rather than decreasing cell proliferation.J Nutr 1997:128:491–7.

    Google Scholar 

  15. Jackson AL, Loeb LA. The mutation rate and cancer.Genetics 1998;148:1483–90.

    PubMed  CAS  Google Scholar 

  16. Payne CM, Crowley C, Washo-Stultz D, et al. The stress-response proteirs poly(ADP-ribose) polymerase and NF-αB protect against bile salt-induced apoptosis.Cell Death Differ 1998;5:623–36.

    Article  PubMed  CAS  Google Scholar 

  17. Payne CM, Bernstein C, Bernstein H. Apoptosis overview emphasizing the role of oxidative stress. DNA damage and signal trans-duction pathways.Leuk Lymphoma 1995:19:43–93.

    PubMed  CAS  Google Scholar 

  18. Boland CR, Martin MA, Goldstein IJ. Lectin reactivities as intermediate biomarkers in premalignant colorectal epithelium.J Cell Biochem Suppl 1992;16G:103–9.

    Article  PubMed  CAS  Google Scholar 

  19. Bresalier RS, Boland CR, Kim YS. Regional differences in normal and cancer-associated glycoconjugates of the human colon.J Natl Cancer Inst 1985;75:249–60.

    PubMed  CAS  Google Scholar 

  20. McLellan EA, Medline A, Bird RP. Sequential analyses of the growth and morphological characteristics of aberrant crypt foci: putative preneoplastic lesions.Cancer Res 1991;51:5270–4.

    PubMed  CAS  Google Scholar 

  21. Pretlow TP, O’Riordan MA, Pretlow TG, Stellato TA. Aberrant crypts in human colonic mucosa: putative preneoplastic lesions.J Cell Biochem Suppl 1992;16G:55–62.

    Article  PubMed  CAS  Google Scholar 

  22. Takayama T, Katsuki S, Takahashi Y, et al. Aberrant crypt foci of the colon as precursors of adenoma and cancer.N Engl J Med 1998;339:1277–84.

    Article  PubMed  CAS  Google Scholar 

  23. Jacobson EL, Jacobson KK. Tissue NAD as a biochemical measure of niacin status in humans.Methods Enzymol 1997;280:221–30.

    Article  PubMed  CAS  Google Scholar 

  24. Jacobson EL, Shieh WM, Huang AC. Mapping the role of NAD metabolism in cancer prevention and treatment.Mol Cell Biochem 1999;193:69–74.

    Article  PubMed  CAS  Google Scholar 

  25. Cherbonnel-Lasserre C, Gauny S, Kronenberg A. Suppression of apoptosis by Bcl-2 or Bcl-xL promotes susceptibility to mutagenesis.Oncogene 1996;13:1489–97.

    PubMed  CAS  Google Scholar 

  26. Liu Y, Naumovski L, Hanawalt P. Nucleotide excision repair capacity is attenuated in human promyelocytic HL60 cells that overexpress Bcl2.Cancer Res 1997;57:1650–3.

    PubMed  CAS  Google Scholar 

  27. Wargovich MJ, Medline A, Bruce WR. Early histopathologic events to evolution of colon cancer in C57BL/6 and CF1 mice treated with 1.2-dimethylhydrazine.J Natl Cancer Inst 1983;71:125–31.

    PubMed  CAS  Google Scholar 

  28. Davies MJ, Bowey EA, Adlercreutz H, Rowland IR, Rumsby PC. Effects of soy or rye supplementation of high-fat diets on colon tumour development in azoxymethane-treated rats.Carcinogenesis 1999;20:927–31.

    Article  PubMed  CAS  Google Scholar 

  29. Roncucci L, Medline A, Bruce WR. Classification of aberrant crypt foci and microadenomas in human colon.Cancer Epidemiol Biomarkers Prev 1991;1:57–60.

    PubMed  CAS  Google Scholar 

  30. Jacobson EL. Niacin deficiency and cancer in women.J Am Coll Nutr 1993;12:412–6.

    PubMed  CAS  Google Scholar 

  31. Jarrett P, Duffill M, Oakley A, Smith A. Pellagra, azathioprine and inflammatory bowel disease.Clin Exp Dermatol 1997;22:44–5.

    Article  PubMed  CAS  Google Scholar 

  32. Cristovao L, Lechner MC, Fidalgo P, Leitao CN, Mira FC, Rueff J. Absence of stimulation of poly(ADP-ribose) polymerase activity in patients predisposed to colon cancer.Br J Cancer 1998;77:1628–32.

    PubMed  CAS  Google Scholar 

  33. Boland CR, Montgomery CK, Kim YS. Alterations in human colonic mucin occurring with cellular differentiation and malignant transformation.Proc Natl Acad Sci U S A 1982;79:2051–5.

    Article  PubMed  CAS  Google Scholar 

  34. Jass JR, Roberton AM. Colorectal mucin histochemistry in health and disease: a critical review.Pathol Int 1994;44:487–504.

    Article  PubMed  CAS  Google Scholar 

  35. Raedler A, Raedler E. The use of lections to study normal differentiation and malignant transformation.J Cancer Res Clin Oncol 1985;109:245–51.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, University of Arizona, Tucson, Arizona

    James A. Warneke MD

  2. Department of Medicine, University of Arizona, Tucson, Arizona

    Harinder Garewal MD, PhD & David L. Earnest MD

  3. Department of Pharmacology and Toxicology, University of Arizona, Tucson, Arizona

    Elaine L. Jacobson PhD

  4. Department of College of Public Health, University of Arizona, Tucson, Arizona

    Denise J. Roe PhD

  5. Department of the Arizona Cancer Center, University of Arizona, Tucson, Arizona

    Harris Bernstein PhD, James A. Warneke MD, Harinder Garewal MD, PhD, David L. Earnest MD, Claire M. Payne PhD, Denise J. Roe PhD, Haiyan Cui PhD & Elaine L. Jacobson PhD

  6. Tucson Veterans Affairs Hospital, Tucson, Arizona

    Harinder Garewal MD, PhD

  7. Department of Cancer Center, University of Kentucky, Lexington, Kentucky

    Elaine L. Jacobson PhD

  8. Department of Microbiology and Immunology, College of Medicine, University of Arizona, 85724, Tucson, AZ

    Harris Bernstein PhD, Hana Holubec MS, Claire M. Payne PhD & Carol Bernstein PhD

Authors
  1. Harris Bernstein PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hana Holubec MS
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James A. Warneke MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Harinder Garewal MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David L. Earnest MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Claire M. Payne PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Denise J. Roe PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Haiyan Cui PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Elaine L. Jacobson PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Carol Bernstein PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carol Bernstein PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bernstein, H., Holubec, H., Warneke, J.A. et al. Patchy field defects of apoptosis resistance and dedifferentiation in flat mucosa of colon resections from colon cancer patients. Annals of Surgical Oncology 9, 505–517 (2002). https://doi.org/10.1007/BF02557276

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02557276

Key words

Search

Navigation