Lunn, J. C.; Kuhnle, G.; Mai, V.; Frankenfeld, C.; Shuker, D.; Glen, R. C.; Goodman, J. M.; Pollock, J. R. A. and Bingham, S. A.
The effect of haem in red and processed meat on the endogenous formation of N-nitroso compounds in the upper gastrointestinal tract.
Carcinogenesis, 28(3) pp. 685–690.
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 -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.
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