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Red Meat Enhances the Colonic Formation of the DNA Adduct O⁶-Carboxymethyl Guanine: Implications for Colorectal Cancer Risk

¹ Diet and Cancer Group, Dunn Human Nutrition Unit, Wellcome Trust/Medical Research Council Building, Cambridge, United Kingdom; ² Pollock and Pool Ltd., Reading, Berkshire, United Kingdom; and ³ Department of Chemistry, The Open University, Walton Hall, Milton Keynes, United Kingdom

Requests for reprints: Sheila A. Bingham, Dunn Human Nutrition Unit, Wellcome Trust/Medical Research Council Building, Cambridge, United Kingdom CB2 2XY. Phone: 44-1223-252760; Fax: 44-1223-252765; E-mail: sab{at}mrc-dunn.cam.ac.uk.

Red meat is associated with increased risk of colorectal cancer and increases the endogenous formation of N-nitrosocompounds (NOC). To investigate the genotoxic effects of NOC arising from red meat consumption, human volunteers were fed high (420 g) red meat, vegetarian, and high red meat, high-fiber diets for 15 days in a randomized crossover design while living in a volunteer suite, where food was carefully controlled and all specimens were collected. In 21 volunteers, there was a consistent and significant (P < 0.0001) increase in endogenous formation of NOC with the red meat diet compared with the vegetarian diet as measured by apparent total NOC (ATNC) in feces. In colonic exfoliated cells, the percentage staining positive for the NOC-specific DNA adduct, O⁶-carboxymethyl guanine (O⁶CMG) was significantly (P < 0.001) higher on the high red meat diet. In 13 volunteers, levels were intermediate on the high-fiber, high red meat diet. Fecal ATNC were positively correlated with the percentage of cells staining positive for O⁶CMG (r² = 0.56, P = 0.011). The presence of O⁶CMG was also shown in intact small intestine from rats treated with the N-nitrosopeptide N-acetyl-N'-prolyl-N'-nitrosoglycine and in HT-29 cells treated with diazoacetate. This study has shown that fecal NOC arising from red meat include direct acting diazopeptides or N-nitrosopeptides able to form alkylating DNA adducts in the colon. As these O⁶CMG adducts are not repaired, and if other related adducts are formed and not repaired, this may explain the association of red meat with colorectal cancer. (Cancer Res 2006; 66(3): 1859-65)

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