Effects of Combination of Calcium and Aspirin on Azoxymethane-Induced Aberrant Crypt Foci Formation in the Colons of Mice and Rats

Abstract

Human intervention studies have suggested an exciting synergistic action between calcium supplementation and aspirin intake in reducing the risk of colorectal cancer. The aim of this study was to determine whether such a synergy can be demonstrated on azoxymethane (AOM)-induced colon aberrant crypt foci (ACF) formation in mice and rats. Female CF-1 mice and male F344 rats were injected subcutaneously with AOM and then received diet treatments for 8 wk. The basal control diet contained high fat (20% mixed lipids by weight) and low calcium (1.4 mg/g diet) to mimic the average Western diet. The treatment diets contained enriched calcium (5.2 mg calcium/g diet), aspirin (0.2 mg aspirin/g diet), or calcium plus aspirin (5.2 mg calcium plus 0.2 mg aspirin/g diet). Treatment with calcium, aspirin, or their combination significantly decreased the number of total ACF and aberrant crypt per mouse (by 43–59%) or rat (by 23–38%), but statistically significant differences among the 3 groups were not observed. A hint of additivity between calcium and aspirin was observed in mice but not in rats. These results indicate that the combination of calcium and aspirin did not produce a synergistic effect on the ACF formation in AOM-treated mice and rats.

ACKNOWLEDGMENTS

This work was supported by National Institute of Health Grants CA88961 and CA37663. Yingying Liu and Jihyeung Ju contributed equally to this study.

Notes

^a Composition is expressed as a percentage by weight.

^b Mixed lipid contains 16% beef tallow, 10% lard, 12% butter fat, 30% hydrogenated soybean oil, 27% corn oil, and 5% peanut oil.

^c Mineral mix contains 8.4% magnesium oxide, 51.5% magnesium sulfate heptahydrate O, 0.4% chromium potassium sulfate, 0.2% cupric carbonate, 0.7% potassium iodate, 4.2% ferric citrate, 2.5% manganous carbonate, 0.7% sodium selenite, 1.1% zinc carbonate, and 31.7% sucrose.

^a Abbreviations are as follows: ACF, aberrant crypt foci; AC, aberrant crypt; AOM, azoxymethane. Female CF-1 mice were treated with 2 weekly subcutaneously (sc) injections of AOM and then maintained on the experimental diet for 8 weeks. Values are means ± SD of the number mice (N) analyzed.

^b Male F344 rats were treated with 2 weekly sc injections of AOM and then maintained on the experimental diet for 8 weeks. Values are mean ± SD of the number of rats (N) analyzed.

^c One-way ANOVA; values with different superscripts (^{+ ≠}) differ significantly (P < 0.05).

^d Fisher exact probability test; P < 0.05.

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^≠Values with different superscripts differ significantly.