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

• Published in: Carcinogenesis (New York) 2007-03, Vol.28 (3), p.685-690
• Main Authors: Lunn, J.C., Kuhnle, G., Mai, V., Frankenfeld, C., Shuker, D.E.G., Glen, R. C., Goodman, J.M., Pollock, J.R.A., Bingham, S.A.
• Format: Article
• Language: English
• Subjects: Animals; Ascorbic Acid - pharmacology; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; Gastric Mucosa - metabolism; Heme - isolation & purification; Heme - pharmacology; Humans; Ileostomy; Ileum - metabolism; Kinetics; Meat - analysis; Meat Products - analysis; Medical sciences; Nitroso Compounds - metabolism; Tumors; Vitamin E - pharmacology
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/bgl192

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 α-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.