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Lynn Vanhaecke, Caroline Rombouts, Thomas Van Hecke, Els Vossen, Stefaan De Smet, Lieselot Y. Hemeryck


Epidemiological research has demonstrated that the consumption of red meat contributes to colorectal cancer (CRC) risk. At the time, the main hypothesis on the red meat-CRC relationship is based on the fact that red, but not white meat consumption, has been linked to CRC, and that red meat contains more heme iron than white meat. More specifically, the heme hypothesis states that the ingestion of heme iron stimulates the formation of N-nitroso compounds (NOCs) and lipid peroxidation products (LPOs). Both NOCs and LPOs can exert geno- as well as cytotoxic effects, and as such contribute to carcinogenesis. In this study, beef (model for red meat) and chicken (model for white meat) were digested in vitro (static model) as well as in vivo (Sprague-Dawley rats) to investigate the gastrointestinal formation of DNA adducts upon red vs. white meat digestion. DNA adduct formation was assessed by means of a state-of-the-art UHPLC-HRMS DNA adductomics platform (Q-ExactiveTM) and in-house DNA adduct database, after which univariate (e.g. t-test) as well as multivariate (e.g. OPLS-DA) statistics were employed for red meat associated DNA adduct marker discovery. Combining the results from 3 independent in vitro and 1 in vivo digestion experiment(s), 7 DNA adduct types, including O6-carboxymethylguanine, dimethyl- or ethylthymine, methylguanine, heptanalguanine, a malondialdehyde-guanine adduct, and a malondialdehyde-cytosine adduct could be singled out as potential red meat digestion markers. This is highly relevant to the red meat-CRC hypothesis because the formation of the retrieved DNA adduct types may be linked to DNA alkylation and/or oxidation by e.g. NOCs and/or LPOs. Therefore, follow-up research should focus on the role of DNA adduct formation in the red meat-CRC pathway, as well as the mutagenic potential and human in vivo relevance of the proposed DNA adduct markers.


colorectal cancer, DNA adductome mapping, gastrointestinal digestion, red meat



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About The Authors

Lynn Vanhaecke

Caroline Rombouts

Thomas Van Hecke

Els Vossen

Stefaan De Smet

Lieselot Y. Hemeryck

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