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Carcinogenesis Advance Access published online on October 19, 2006

Carcinogenesis, doi:10.1093/carcin/bgl192
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© The Author 2006. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Received June 29, 2006
Revised August 31, 2006
Accepted October 5, 2006

MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION

The effect of haem in red and processed meat on the endogenous formation of N-nitroso compounds in the upper gastrointestinal tract

J. C. Lunn 1, G. Kuhnle 1, V. Mai 2, C. Frankenfeld 3, D. E. G. Shuker 4, R. C. Glen 5, J. M. Goodman 5, J. R. A. Pollock 6, and S. A. Bingham 1 *

1 MRC Dunn Human Nutrition Unit, MRC/Wellcome Trust Building, Cambridge, UK, CB2 2XY
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
4 Department of Chemistry, The Open University, Milton Keynes, UK
5 The Unilever Centre for Molecular Sciences Informatics, University of Cambridge, Cambridge, UK
6 Pollock and Pool Ltd, Woodley, Reading, Berkshire, UK, RG5 4DX

* To whom correspondence should be addressed.
S. A. Bingham, E-mail: sheila.bingham{at}mrc-dunn.cam.ac.uk


   Abstract

Red and processed meat consumption increases the risk of large bowel cancer and it has been demonstrated that haem in red meat 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 240g red meat or 240g processed meat 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 22µg ATNC/kg (red meat) and 37µg ATNC/kg (processed meat), and 9µg ATNC/kg in the no meat diet. Levels significantly increased to 1175µg ATNC/kg (standard error of the mean (SEM) = 226µg ATNC/kg) following the red meat (p = 0.001) and 1832µg ATNC/kg (SEM = 294µg ATNC/kg) following processed meat (p < 0.001) compared to the no meat diet (283µg ATNC/kg, SEM = 74µg ATNC/kg). ATNC concentrations in the ileal output were equivalent to those measured in faeces in similarly designed feeding studies. Supplementation with either 1mg ascorbic acid or 400IU {alpha}-tocopherol, had no effect on the concentration of ATNC detected in the ileal output. In in vitro experiments, N-nitrosomorpholine 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.

Keywords: colorectal cancer; red meat; nitrosyl haem; apparent total N-nitroso compounds.
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