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Carcinogenesis Advance Access originally published online on June 4, 2009
Carcinogenesis 2009 30(8):1402-1407; doi:10.1093/carcin/bgp130
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Effect of processed and red meat on endogenous nitrosation and DNA damage

Annemiek M.C.P. Joosen*, Gunter G.C. Kuhnle, Sue M. Aspinall, Timothy M. Barrow, Emmanuelle Lecommandeur, Amaya Azqueta1, Andrew R. Collins1 and Sheila A. Bingham

MRC Dunn Human Nutrition Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 0XY, UK
1 Department of Nutrition, Faculty of Medicine, University of Oslo, 0316 Oslo, Norway

* To whom correspondence should be addressed. Tel: +44 1223 252 762; Fax: +44 1223 252 765; Email: amj{at}mrc-mbu.cam.ac.uk

Haem in red meat (RM) stimulates the endogenous production of mutagenic nitroso compounds (NOC). Processed (nitrite-preserved red) meat additionally contains high concentrations of preformed NOC. In two studies, of a fresh RM versus a vegetarian (VEG) diet (six males and six females) and of a nitrite-preserved red meat (PM) versus a VEG diet (5 males and 11 females), we investigated whether processing of meat might increase colorectal cancer risk by stimulating nitrosation and DNA damage. Meat diets contained 420 g (males) or 366 g (females) meat/per day. Faecal homogenates from day 10 onwards were analysed for haem and NOC and associated supernatants for genotoxicity. Means are adjusted for differences in male to female ratios between studies. Faecal NOC concentrations on VEG diets were low (2.6 and 3.5 mmol/g) but significantly higher on meat diets (PM 175 ± 19 nmol/g versus RM 185 ± 22 nmol/g; P = 0.75). The RM diet resulted in a larger proportion of nitrosyl iron (RM 78% versus PM 54%; P < 0.0001) and less nitrosothiols (RM 12% versus PM 19%; P < 0.01) and other NOC (RM 10% versus PM 27%; P < 0.0001). There was no statistically significant difference in DNA breaks induced by faecal water (FW) following PM and RM diets (P = 0.80). However, PM resulted in higher levels of oxidized pyrimidines (P < 0.05). Surprisingly, VEG diets resulted in significantly more FW-induced DNA strand breaks than the meat diets (P < 0.05), which needs to be clarified in further studies. Meats cured with nitrite have the same effect as fresh RM on endogenous nitrosation but show increased FW-induced oxidative DNA damage.

Abbreviations: CI, confidence interval; EDTA, ethylenediaminetetraacetic acid; EndoIII, endonuclease III; FW, faecal water; FeNO, nitrosyl iron; FPG, formamidopyrimidine; MTT, mean transit time; NOC, nitroso compounds; PM, processed (nitrite-preserved red) meat; RM, red meat; RSNO, nitrosothiols; VEG, vegetarian

Received March 24, 2009; revised May 8, 2009; accepted May 19, 2009.


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