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Calcium supplementation and Aspirin have been shown to suppress colon carcinogenesis. The aim of the present study was to investigate whether the combination of calcium and Aspirin will generate a synergistic effect on aberrant crypt foci (ACF) formation in an azoxymethane (AOM)-induced colon tumorigenesis mouse model. Forty female CF-1 mice were randomly divided into 4 groups (10 mice in each group) and injected subcutaneously with AOM 10 mg/kg body weight once a week for two consecutive weeks at ages of 5 and 6 weeks. The basic control diet, a high-fat (20% mixed lipids by weight), low-calcium (1.4 mg /g diet) diet, was formulated to mimic the average Western diet. Three days after the last injection, mice were given a calcium-enriched diet (5.2 mg calcium/g diet), Aspirin-enriched diet (0.2 mg Aspirin/g diet), combination diet (5.2 mg calcium and 0.2 mg Aspirin/g diet) or control diet for 8 weeks until the experiment was terminated. Fixed colon tissues were stained with methylene blue, and the number of ACF containing single or multi-AC was scored under the microscope. Both calcium and Aspirin significantly decreased the total number of ACF/colon by 43% (P<0.05) and 40% (P<0.05), respectively. Combination of calcium and Aspirin significantly decreased number of ACF/colon by 50% (P<0.05). However, statistically significant differences among the extents of inhibition in different groups were not observed. We found a more prominent decrease in the number of large foci (≥3 crypts/foci) than the number of small foci (< 3crypts/foci) by all of the treatments: calcium, Aspirin, and their combination decreased the number of large foci by 58%, 66%, and 79%, respectively (P<0.05). These results suggest that calcium and Aspirin have an additive effect in inhibiting colon carcinogenesis. Further studies are required to better characterize the effect (Supported by NIH grant CA 88961).

[Proc Amer Assoc Cancer Res, Volume 47, 2006]

American Association for Cancer Research
2006