Carcinogenesis Advance Access originally published online on October 19, 2006
Carcinogenesis 2007 28(3):685-690; doi:10.1093/carcin/bgl192
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The effect of haem in red and processed meat on the endogenous formation of N-nitroso compounds in the upper gastrointestinal tract
1 MRC Dunn Human Nutrition Unit, MRC/Wellcome Trust Building Cambridge, CB2 2XY, UK
2 Department of Epidemiology and Preventive Medicine, University of Maryland Medical School Baltimore, MD 21201, USA
3 Division of Cancer Epidemiology and Genetics, National Cancer Institute Bethesda, MD, USA
4 The Unilever Centre for Molecular Sciences Informatics, University of Cambridge Cambridge, UK
5 Department of Chemistry, The Open University Milton Keynes, UK
6 Pollock and Pool Ltd, Woodley Reading, Berkshire, RG5 4DX, UK
*To whom correspondence should be addressed at: Medical Research Council, Dunn Human Nutrition Unit, Wellcome Trust/MRC Building, Cambridge CB2 2XY, UK. Tel: +44 1223 252760; Fax: +44 1223 252765; Email: sheila.bingham{at}mrc-dunn.cam.ac.uk
Red and processed meat (PM) consumption increases the risk of large bowel cancer and it has been demonstrated that haem in red meat (RM) stimulates the endogenous production of N-nitroso compounds (NOCs) within the human intestine. To investigate whether N-nitrosation occurs in the upper gastrointestinal tract, 27 ileostomists were fed diets containing no meat, or 240 g RM or 240 g PM in a randomly assigned crossover intervention design carried out in a volunteer suite. Endogenous NOC were assessed as apparent total N-nitroso compounds (ATNC) in the ileostomy output. ATNC concentration in the diets was 22 µg ATNC/kg (RM) and 37 µg ATNC/kg (PM), and 9 µg ATNC/kg in the no meat diet. Levels significantly increased to 1175 µg ATNC/kg SEM = 226 µg ATNC/kg) following the RM (P = 0.001) and 1832 µg ATNC/kg (SEM = 294 µg ATNC/kg) following PM (P < 0.001) compared to the no meat diet (283 µg ATNC/kg, SEM = 74 µg ATNC/kg). ATNC concentrations in the ileal output were equivalent to those measured in faeces in similarly designed feeding studies. Supplementation with either 1 g ascorbic acid or 400 IU 
-tocopherol had no effect on the concentration of ATNC detected in the ileal output. In in vitro experiments, N-nitrosomorpholine (NMor) was formed in the presence of nitrosated haemoglobin, at pH 6.8 but not in the absence of nitrosated haemoglobin. These findings demonstrate that haem may facilitate the formation of NOC in the absence of colonic flora in the upper human gastrointestinal tract.
Abbreviations: NOC, N-nitroso compound; ATNC, apparent total N-nitroso compounds; RM, red meat; PM, processed meat; NMor, N-nitrosomorpholine
Received June 29, 2006; revised August 31, 2006; accepted October 5, 2006.