H Mori, Y Yamada, Y Hirose, T Kuno, M Katayama, K Sakata, K Yoshida, S Sugie, A Hara, N Yoshimi

Control of cell proliferation is important for cancer prevention since cell proliferation has essential roles in carcinogenesis in the processes of both initiation and promotion. In large bowel carcinogenesis, carcinogens produce hyperproliferation of cells in the target sites and the cell proliferation persists even after the cessation of carcinogen exposure. Chemopreventive agents principally control the increased cell proliferation when given in the initiation as well as post-initiation phases. Aberrant crypt foci (ACF) which appear soon after carcinogen exposure in large bowel carcinogenesis in rodents have been used as a reliable biomarker for screening of potential chemopreventive agents. Recently, our group demonstrated the presence of probable premalignant lesions with frequent b-catenin gene mutations and accumulation of the corresponding protein in the colonic epithelium of rats given a large bowel carcinogen. Such early-appearing lesions lack the morphological appearance of ACF. Expression of these b-catenin-accumulated crypts (BCAC) is markedly suppressed by a chemopreventive cyclooxygenase-2 inhibitor, celecoxib. BCAC are suggested to be more reliable biomarkers than ACF for screening effective chemopreventive agents for colorectal cancer and for investigating the mode of action of the agents.

Key words: Chemoprevention, colon carcinogenesis, b-catenin, cell proliferation, crypt lesion

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