Risk factors for colorectal cancer in man induce aberrant crypt foci in rats: Preliminary findings

Epidemiological studies have demonstrated clear associations between specific dietary and environmental risk factors and incidence of colorectal cancer. The mechanisms responsible for these associations are not known though it has been suggested that they involve the formation of endogenous cytotoxins , genotoxins, and proliferative factors and changes in the colonic epithelium such as aberrant crypt foci (ACF). Methods: Rats were provided with diets that simulated the risk factors for CRC - low calcium and low vitamin D, high iron, high fructose, and decreased light (UV) exposure – or a control diet for 16 or 40 weeks and assessed with biochemical measures and for colonic topological and histological evidence of colon carcinogenesis. Results: Circulating ionized calcium was decreased from 2.85 to 1.69 mmol/L, and heterogeneous, non-dysplastic ACF were increased from 0.7 to 13.6 lesions/colon (both p < 0.001). Conclusion: Rats exposed to environmental conditions associated with colon cancer develop colonic lesions similar to those in rats exposed to the non-genotoxic colon carcinogen, dextransulfate sodium and to the most frequently observed ACF in the human colon. The rodent model could be used to assess the pathways to colon cancer and to provide guidance for clinical studies.