These authors contributed equally to this work (shared first author).
O6-carboxymethylguanine DNA adduct formation and lipid peroxidation upon in vitro gastrointestinal digestion of haem-rich meat
Article first published online: 2 JUL 2014
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 58, Issue 9, pages 1883–1896, September 2014
How to Cite
Bussche, J. V., Hemeryck, L. Y., Van Hecke, T., Kuhnle, G. G. C., Pasmans, F., Moore, S. A., Van de Wiele, T., De Smet, S. and Vanhaecke, L. (2014), O6-carboxymethylguanine DNA adduct formation and lipid peroxidation upon in vitro gastrointestinal digestion of haem-rich meat. Mol. Nutr. Food Res., 58: 1883–1896. doi: 10.1002/mnfr.201400078
- Issue published online: 8 SEP 2014
- Article first published online: 2 JUL 2014
- Manuscript Accepted: 14 MAY 2014
- Manuscript Revised: 15 APR 2014
- Manuscript Received: 5 FEB 2014
- Federal Public Service of Health, Food Chain Safety and Environment. Grant Number: RT 11/6250 MEATNOX
- In vitro gastrointestinal digestion;
- Meat consumption;
- N-nitroso compounds;
Epidemiological and clinical studies have demonstrated that the consumption of red haem-rich meat may contribute to the risk of colorectal cancer. Two hypotheses have been put forward to explain this causal relationship, i.e. N-nitroso compound (NOC) formation and lipid peroxidation (LPO).
Methods and Results
In this study, the NOC-derived DNA adduct O6-carboxymethylguanine (O6-CMG) and the LPO product malondialdehyde (MDA) were measured in individual in vitro gastrointestinal digestions of meat types varying in haem content (beef, pork, chicken). While MDA formation peaked during the in vitro small intestinal digestion, alkylation and concomitant DNA adduct formation was observed in seven (out of 15) individual colonic digestions using separate faecal inocula. From those, two haem-rich meat digestions demonstrated a significantly higher O6-CMG formation (p < 0.05). MDA concentrations proved to be positively correlated (p < 0.0004) with haem content of digested meat. The addition of myoglobin, a haem-containing protein, to the digestive simulation showed a dose–response association with O6-CMG (p = 0.004) and MDA (p = 0.008) formation.
The results suggest the haem-iron involvement for both the LPO and NOC pathway during meat digestion. Moreover, results unambiguously demonstrate that DNA adduct formation is very prone to inter-individual variation, suggesting a person-dependent susceptibility to colorectal cancer development following haem-rich meat consumption.