Carcinogenesis Advance Access published online on October 4, 2007
Carcinogenesis, doi:10.1093/carcin/bgm216
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High Red Meat Diets Induce Greater Numbers of Colonic DNA Double-Strand Breaks than White Meat in Rats: Attenuation by High Amylose Maize Starch
1 CSIRO Human Nutrition, Kintore Avenue, Adelaide, Australia
2 Food Futures National Research Flagship, Australia
3 Preventative Health National Research Flagship, Australia
4 Discipline of Physiology, School of Molecular Science, University of Adelaide, Adelaide, Australia
* To whom request for reprints and correspondence should be addressed at: CSIRO Human Nutrition, PO Box 10041 Adelaide, SA 5000, Australia. Telephone: +61 8 8303 8909 Fax: +61 8 8303 8899 e-mail: michael.conlon{at}csiro.au
Human population studies show that dietary red and processed, but not white, meats are associated with increased risk of colorectal cancer but dietary fibre appears to be protective. We examined whether dietary cooked red or white meat had differential effects on colonic DNA damage in rats and if resistant starch (RS), a dietary fibre component, provided protection. Rats were fed diets containing 15, 25 or 35% of cooked beef or chicken, both with or without 20% high amylose maize starch (HAMS) as a source of RS, for four weeks. DNA single-strand (SSB) and double-strand breaks (DSB) were measured in isolated colonocytes (by comet assay) along with apoptosis levels, colonic mucus thickness and large bowel short chain fatty acids (SCFA). Both red and white meat increased colonocyte SSB and DSB dose-dependently but damage was substantially greater with red meat. Dietary HAMS prevented these increases. Apoptotic cell numbers were increased dose-dependently by red meat irrespective of HAMS feeding, whereas white meat only increased apoptotic cell numbers in the presence of HAMS. Red meat induced greater colonic mucus layer thinning than white meat but HAMS was protective in both cases. HAMS induced increases in large bowel SCFA, including butyrate, and significantly lowered concentrations of phenols and cresols. We have demonstrated that dietary red meat causes greater levels of colonic DNA SSB and DSB than white meat, consistent with the epidemiological data. Dietary RS protects against this damage and also against loss of the mucus barrier, probably through increased butyrate production.
Key Words: Resistant Starch • Short Chain Fatty Acids • Red meat • White meat • Colon • DNA damage
Received July 18, 2007; revised September 13, 2007; accepted September 14, 2007.