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

Lewin, Michelle H.; Bailey, Nina; Bandaletova, Tanya; Bowman, Richard; Cross, Amanda J.; Pollock, Jim; Shuker, David E.G. and Bingham, Sheila A. (2006). Red Meat Enhances the Colonic Formation of the DNA Adduct O6-Carboxymethyl Guanine: Implications for Colorectal Cancer Risk. Cancer Research, 66(3) pp. 1859–1865.

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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, highfiber 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-NV-prolyl-NV-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).

Item Type: Journal Article
ISSN: 0008-5472
Extra Information: Some of the symbols may not have transferred correctly into this bibliographic record and/or abstract.
Keywords: Coloreactal cancer; O6-carboxymethylguanine; DNA adducts
Academic Unit/Department: Science > Life, Health and Chemical Sciences
Item ID: 1194
Depositing User: David Shuker
Date Deposited: 01 Jun 2006
Last Modified: 14 Jan 2016 15:44
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