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Commentary to:Enhanced acute apoptotic response to azoxymethane-induced DNA damage in the rodent colonic epithelium by Tyrian purple precursors: A potential colorectal cancer chemopreventativeChantel B. Westley, Cassandra M. McIver, Catherine A. Abbott, Richard K. Le Leu and Kirsten Benkendorff

Previous studies have shown increased levels of colonocyte DNA damage (as measured by the comet assay) and thinning of the colonic mucus layer in rats fed higher dietary protein as casein or red meat with highly digestible starch. Feeding resistant starch (RS) as high amylose maize starch (HAMS) opposed these changes. However, the dietary level of HAMS was relatively high (48% by weight) so this study was conducted to establish whether HAMS had the same effects at lower dietary levels. Adult male rats were fed a diet containing 25% casein with 0%, 10%, 20%, 30% or 40% HAMS for 4 wk. DNA single strand breaks and 8-hydroxyguanosine levels were measured in isolated colonocytes by the comet assay. As expected, comet tail moment was greatest and the mucus barrier thinnest in rats fed 0% HAMS. DNA damage was reduced and the mucus barrier thickened in a logarithmic dose-dependent manner by HAMS. There was no significant difference in 8-hydroxyguanosine between dietary groups. Caecal and fecal short chain fatty acid (SCFA) pools rose with the increased level of dietary HAMS. DNA damage of colonocytes correlated negatively with caecal SCFA but the strongest correlation was with caecal butyrate, which is consistent with the proposed role of this SCFA in promoting a normal cell phenotype. These data show that HAMS prevents protein-induced colonic DNA damage in a dose-dependent manner. Inclusion of 10% HAMS was found to be sufficient to oppose colonocyte DNA damage, and to increase caecal and fecal SCFA pools.

In a previous study we have shown that high levels of dietary protein (as casein) result in increased levels of colonic DNA damage, measured by the comet assay, and thinning of the colonic mucus layer in rats when dietary resistant starch (RS) is negligible. Feeding RS abolishes these effects. This study aimed to establish whether a diet high in protein as cooked red meat would have similar effects and whether RS was protective. Rats were fed a diet containing 15% or 25% casein or 25% cooked lean red beef, each with or without the addition of 48% high amylose maize starch (a rich source of RS) for four weeks. As expected, high dietary casein caused a 2-fold increase in colonic DNA damage compared with a low casein diet and reduced the thickness of the colonic mucus layer by 41%. High levels of cooked meat caused 26% greater DNA damage than the high casein diet but reduced mucus thickness to a similar degree to casein. Addition of RS to the diet abolished the increase in DNA damage and the loss of colonic mucus thickness induced by either high protein diet. Cecal and fecal short chain fatty acid pools were also increased by inclusion of RS in the diet. Because DNA damage is an early step in the initiation of cancer, these findings suggest that increased DNA damage due to high dietary protein as cooked red meat or casein could increase colorectal cancer risk but inclusion of resistant starch in the diet could significantly reduce that risk.