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Carcinogenesis Advance Access published online on June 4, 2009
Carcinogenesis, 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. Joosen1, Gunter G.C. Kuhnle1, Sue Aspinall1, Timothy M. Barrow1, Emmanuelle Lecommandeur1, Amaya Azqueta2, Andrew Collins2 and Sheila A. Bingham1

1 MRC Dunn Human Nutrition Unit, Cambridge, United Kingdom
2 Department of Nutrition, Faculty of Medicine, University of Oslo, Oslo, Norway

Corresponding author: Annemiek M.C.P. Joosen, MRC Dunn Human Nutrition Unit, Wellcome Trust/MRC Building, Hills Road, Cambridge CB2 0XY, United Kingdom, Phone: +44 (0)1223 252 762, Fax: +44 (0)1223 252 765, E-mail: amj{at}mrc-mbu.cam.ac.uk

Haem in red meat stimulates the endogenous production of mutagenic nitrosocompounds (NOC). Processed meat additionally contains high concentrations of preformed NOC. In two studies, of a fresh red meat (RM) versus a vegetarian diet (6 males, 6 females), and of a nitrite preserved red meat (PM) versus a vegetarian diet (5 males, 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/d. 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 vegetarian diets were low (2.6 and 3.5 mmol/g) but significantly higher on meat diets, (PM 175±19 nmol/g vs RM 185±22 nmol/g, P = 0.75). The RM diet resulted in a larger proportion of nitrosyl iron (RM 78% vs PM 54%; P<0.0001) and less nitrosothiols (RM 12% vs PM 19%; P<0.01) and other NOC (RM 10% vs PM 27%; P<0.0001). There was no statistically significant difference in DNA breaks induced by faecal water following PM and RM diets (P=0.80). However, PM resulted in higher levels of oxidized pyrimidines (P<0.05). Surprisingly, vegetarian diets resulted in significantly more faecal water-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 red meat on endogenous nitrosation, but show increased faecal water-induced oxidative DNA damage.

Key Words: diet • nitroso compounds • comet assay • colon

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


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