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In vitro DNA adduct profiling to mechanistically link red meat consumption to colon cancer promotion

(2016) TOXICOLOGY RESEARCH. 5(5). p.1346-1358
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Abstract
Colorectal cancer (CRC) is the third most common cancer type in the world. Epidemiological research has demonstrated that both red and processed meat consumption significantly contribute to CRC risk. In this study, red meat toxicity was investigated by means of simulated gastrointestinal conditions, malondialdehyde (MDA) analysis and UHPLC-(HR) MS(/MS) based DNA adductomics. Since dairy products with high calcium content are associated with a decreased CRC-risk, the possible CRC-protective effects of calcium were assessed as well. The obtained results confirmed the earlier reported finding that heme-rich meat stimulates lipid peroxidation and O-6-carboxymethylguanine (O-6-CMG) DNA adduct formation during digestion. Calcium carbonate (CaCO3) supplementation resulted in both toxic and anti-toxic effects; i.e. stimulation of O-6-CMG production, but reduction of MDA formation. DNA adductome mapping of meat digests revealed a significant interindividual variability. The observed DNA adduct profile also differed according to the digested meat type, uncovering different putative DNA adducts that seem to be associated with digestion of beef or chicken with or without supplemented CaCO3. Formamidopyrimidine-adenine was found to be discriminative for meat digests without added CaCO3, carboxyethyl-cytosine was significantly higher in beef digests and methoxymethylcytosine (or its hydroxyethylcytosine isomer) was found to be lower in meat digests supplemented with CaCO3. These results demonstrate that DNA adduct formation may be involved in the pathway that links red meat digestion to CRC promotion. In addition, the possible CRC-protective attributes of calcium through anti-oxidant actions could be documented.
Keywords
N-NITROSO COMPOUNDS, COLORECTAL-CANCER, LIPID-PEROXIDATION, MASS-SPECTROMETRY, BEEF MEAT, CALCIUM, DAMAGE, DIGESTION, MALONDIALDEHYDE, DIET

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Chicago
Hemeryck, Lieselot, Caroline Rombouts, Thomas Van Hecke, Lieven Van Meulebroek, Julie Vandenbussche, Stefaan De Smet, and Lynn Vanhaecke. 2016. “In Vitro DNA Adduct Profiling to Mechanistically Link Red Meat Consumption to Colon Cancer Promotion.” Toxicology Research 5 (5): 1346–1358.
APA
Hemeryck, L., Rombouts, C., Van Hecke, T., Van Meulebroek, L., Vandenbussche, J., De Smet, S., & Vanhaecke, L. (2016). In vitro DNA adduct profiling to mechanistically link red meat consumption to colon cancer promotion. TOXICOLOGY RESEARCH, 5(5), 1346–1358.
Vancouver
1.
Hemeryck L, Rombouts C, Van Hecke T, Van Meulebroek L, Vandenbussche J, De Smet S, et al. In vitro DNA adduct profiling to mechanistically link red meat consumption to colon cancer promotion. TOXICOLOGY RESEARCH. 2016;5(5):1346–58.
MLA
Hemeryck, Lieselot, Caroline Rombouts, Thomas Van Hecke, et al. “In Vitro DNA Adduct Profiling to Mechanistically Link Red Meat Consumption to Colon Cancer Promotion.” TOXICOLOGY RESEARCH 5.5 (2016): 1346–1358. Print.
@article{8518044,
  abstract     = {Colorectal cancer (CRC) is the third most common cancer type in the world. Epidemiological research has demonstrated that both red and processed meat consumption significantly contribute to CRC risk. In this study, red meat toxicity was investigated by means of simulated gastrointestinal conditions, malondialdehyde (MDA) analysis and UHPLC-(HR) MS(/MS) based DNA adductomics. Since dairy products with high calcium content are associated with a decreased CRC-risk, the possible CRC-protective effects of calcium were assessed as well. The obtained results confirmed the earlier reported finding that heme-rich meat stimulates lipid peroxidation and O-6-carboxymethylguanine (O-6-CMG) DNA adduct formation during digestion. Calcium carbonate (CaCO3) supplementation resulted in both toxic and anti-toxic effects; i.e. stimulation of O-6-CMG production, but reduction of MDA formation. DNA adductome mapping of meat digests revealed a significant interindividual variability. The observed DNA adduct profile also differed according to the digested meat type, uncovering different putative DNA adducts that seem to be associated with digestion of beef or chicken with or without supplemented CaCO3. Formamidopyrimidine-adenine was found to be discriminative for meat digests without added CaCO3, carboxyethyl-cytosine was significantly higher in beef digests and methoxymethylcytosine (or its hydroxyethylcytosine isomer) was found to be lower in meat digests supplemented with CaCO3. These results demonstrate that DNA adduct formation may be involved in the pathway that links red meat digestion to CRC promotion. In addition, the possible CRC-protective attributes of calcium through anti-oxidant actions could be documented.},
  author       = {Hemeryck, Lieselot and Rombouts, Caroline and Van Hecke, Thomas and Van Meulebroek, Lieven and Vandenbussche, Julie and De Smet, Stefaan and Vanhaecke, Lynn},
  issn         = {2045-452X},
  journal      = {TOXICOLOGY RESEARCH},
  keyword      = {N-NITROSO COMPOUNDS,COLORECTAL-CANCER,LIPID-PEROXIDATION,MASS-SPECTROMETRY,BEEF MEAT,CALCIUM,DAMAGE,DIGESTION,MALONDIALDEHYDE,DIET},
  language     = {eng},
  number       = {5},
  pages        = {1346--1358},
  title        = {In vitro DNA adduct profiling to mechanistically link red meat consumption to colon cancer promotion},
  url          = {http://dx.doi.org/10.1039/c6tx00079g},
  volume       = {5},
  year         = {2016},
}

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