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Azoxymethane-induced rat aberrant crypt foci: Relevance in studying chemoprevention of colon cancer

Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch, Health Canada, C218 Banting Building, Postal Locator 2202D, Ottawa, K1A 0L2, Ontario, Canada.
World Journal of Gastroenterology (Impact Factor: 2.43). 12/2008; 14(43):6632-5. DOI: 10.3748/wjg.14.6632
Source: PubMed

ABSTRACT The pathogenesis of colon cancer involves sequential and multistep progression of epithelial cells initiated to a cancerous state with defined precancerous intermediaries. Aberrant crypt foci (ACF) represent the earliest identifiable intermediate precancerous lesions during colon carcinogenesis in both laboratory animals and humans. ACF are easily induced by colon-specific carcinogens in rodents and can be used to learn more about the process of colon carcinogenesis. For over two decades, since its first discovery, azoxymethane (AOM)-induced rodent ACF have served as surrogate biomarkers in the screening of various anticarcinogens and carcinogens. Several dietary constituents and phytochemicals have been tested for their colon cancer chemopreventive efficacy using the ACF system. There has been substantial effort in defining and refining ACF in terms of understanding their molecular make-up, and extensive research in this field is currently in progress. In chemoprevention studies, AOM-induced rat ACF have been very successful as biomarkers, and have provided several standardized analyses of data. There have been several studies that have reported that ACF data do not correlate to actual colon tumor outcome, however, and hence there has been an ambiguity about their role as biomarkers. The scope of this mini-review is to provide valuable insights and limitations of AOM-induced rat ACF as biomarkers in colon cancer chemoprevention studies. The role of the dynamics and biological heterogeneity of ACF is critical in understanding them as biomarkers in chemoprevention studies.

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    • "Although ACF incidence is related to colon carcinogenesis, these preneoplastic lesions are heterogeneous and have different molecular characteristics (Raju, 2008). Thus, ACF with 1, 2 or 3 crypts per focus may regress over time, and those with greater multiplicity (ACF ≥ 4 crypts) may progress to form colon neoplasia and are therefore considered more aggressive (Magnuson et al., 1993; Perše and Cerar, 2011; Raju, 2008). In the present study, TB treatment reduced the ACF ≥ 4 crypts, suggesting that TB acts on more aggressive, aberrant crypt foci and reinforcing its role as an important chemopreventive agent in colon carcinogenesis. "
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