O6-carboxymethylguanine DNA adduct formation and lipid peroxidation upon in vitro gastrointestinal digestion of haem-rich meat

Authors

  • Julie Vanden Bussche,

    Corresponding author
    1. Laboratory of Chemical Analysis, Department of Veterinary Public Health and Food Safety, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
    • Correspondence: Dr. Julie Vanden Bussche, Laboratory of Chemical Analysis, Department of Veterinary Public Health and Food Safety, Faculty of Veterinary Medicine, Ghent University, Merelbeke 9820, Belgium

      E-mail: Julie.VandenBussche@UGent.be

      Fax: +32-9-2647492

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    • These authors contributed equally to this work (shared first author).

  • Lieselot Y. Hemeryck,

    1. Laboratory of Chemical Analysis, Department of Veterinary Public Health and Food Safety, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
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    • These authors contributed equally to this work (shared first author).

  • Thomas Van Hecke,

    1. Laboratory of Animal Nutrition and Animal Product Quality, Department of Animal Production, Faculty of Bioscience Engineering, Ghent University, Melle, Belgium
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  • Gunter G. C. Kuhnle,

    1. Department of Food and Nutritional Sciences, University of Reading, Reading, UK
    2. Department of Public Health and Primary Care, MRC Centre for Nutritional Epidemiology in Cancer Prevention & Survival, University of Cambridge, Cambridge, UK
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  • Frank Pasmans,

    1. Faculty of Veterinary Medicine, Department of Pathology, Bacteriology and Poultry Diseases, Ghent University, Merelbeke, Belgium
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  • Sharon A. Moore,

    1. School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK
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  • Tom Van de Wiele,

    1. Laboratory of Microbial Ecology and Technology, Department of Biochemical and Microbial Technology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium
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  • Stefaan De Smet,

    1. Laboratory of Animal Nutrition and Animal Product Quality, Department of Animal Production, Faculty of Bioscience Engineering, Ghent University, Melle, Belgium
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  • Lynn Vanhaecke

    1. Laboratory of Chemical Analysis, Department of Veterinary Public Health and Food Safety, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
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Abstract

Scope

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.

Conclusion

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.

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