The potential of soy isoflavones (SIs) to reduce colon cancer has been investigated in animal models. These studies have found that outcomes are variable and depend on SI dose. The present study investigated dose-response effects of SIs on colon carcinogenesis in a chemically induced rat cancer model. Sprague-Dawley male rats were injected with 1,2-dimethylhydrazine (DMH) and were provided experimental diets that contained 0, 10, 50, 150, or 500 mg of SI aglycones/kg of diet for 12 weeks. Plasma concentrations of genistein, daidzein, and equol were determined using time-resolved fluoroimmunoassay. Plasma concentrations of these SIs tended to increase in a dose-dependent manner in DMH-treated rats. The numbers of aberrant crypt foci (ACF) and the expression of cyclooxygenase-2 (COX-2) proteins of colons were significantly decreased in the SI-fed groups compared with the control group; however, suppression was not dose-dependent. Furthermore, there were no significant correlations between plasma SI concentrations and ACF or COX-2 expression. Increased SI intake and increased plasma levels of SIs and metabolites were not associated with tissue levels of lipid peroxidation. We conclude that dietary supplementation of SIs suppresses DMH-induced ACF formation and COX-2 expression in a dose-independent manner.

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Soy isoflavones have received considerable attention for the potential role in reducing the risk of cancers. We previously observed significant reduction in the number of colonic aberrant crypt foci and expression of cyclooxygenase‐2 in rats which were fed soy isoflavones after injection of dimethylhydrazine (DMH) for 12 weeks. In this study, we investigated whether feeding soy isoflavones before and during treatment with DMH affects aberrant crypt foci formation and DNA damage in colon. Four weeks old Sprague Dawley male rats were fed AIN93‐based experimental diets supplemented with 0 (control diet), 50 or 500 mg soy isoflavones per kg diet for 8 weeks, and received subcutaneous injections of DMH (20mg/kg body weight) twice per week for 4 weeks while maintaining experimental diets. Then all the groups were given the control diet for another 6 weeks. Colon cells were isolated and subjected to the alkaline single cell gel electrophoresis. DNA damage was determined by measuring tail lengths of the cells with fluorescence microscope. There was no significant difference in weight gains and food efficiencies among groups. Numbers of total aberrant crypts and aberrant crypt foci of colon tended to be lower in the rats pre‐fed soy isoflavones as compared with the control group. DNA damages of colonic cells were insignificant among the groups. Being considered that rats were sacrificed at only 6 weeks after DMH treatment, the results indicate that intake of soy isoflavones before and during DMH treatment may reduce formation of aberrant crypt foci in colon, which was irrelevant to colonic cell DNA damage. This research was supported by RIC program of MCIE.

We have investigated whether soy isoflavones supplemented to diets increase plasma concentrations of soy isoflavones and equol, and whether increased plasma concentration of soy isoflavones suppresses tissue levels of lipid peroxides and aberrant crypt foci (ACF) formation in colon cancer model rats. Sprague Dawley male rats were injected with 1,2‐dimethylthydrazine (DMH) and given one of AIN93‐based experimental diets (0, 10, 50, 150, or 500 mg isoflavones per kg diet) for 12 weeks. Thiobarbituric acid reactive substances (TBARS) of plasma and homogenates of liver and kidneys were determined using TBARS assay kit. Plasma concentrations of genistein, daidzein and equol were determined using kits by competitive time‐resolved fluoroimmunoassay technique. Plasma concentrations of genistein (R2=0.521 by genistein intake, p<0.001), daidzein (R2=0.623 by daidzein intake, p<0.001) and equol (R2=0.528 by daidzein intake, p<0.001) were increased dose‐dependently. However, the numbers of ACF decreased significantly (p<0.01) in 10 or 50 mg isoflavones‐fed groups as compared with the control group, and there was no significant correlation between the number of ACF and plasma concentration of genistein, daidzein or equol. Plasma TBARS level was not influenced by either dose or plasma level of soy isoflavones. Hepatic levels of TBARS were significantly lower in 10 and 50 mg isoflavones‐fed groups as compared with the control group. The level of kidney TBARS was significantly lower in only 50 mg isoflavones‐fed group as compared with the control group. Therefore, the results indicate that optimal level of soy isoflavones seemed to be most effective in suppressing ACF formation and lipid peroxidation in DMH‐induced colon cancer model rats.