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Diet-induced endogenous formation of nitroso compounds in the GI tract
Abstract
Red or processed meat, but not white meat or fish, is associated with colorectal cancer. The endogenous formation of nitroso compounds is a possible explanation, as red or processed meat--but not white meat or fish--causes a dose-dependent increase in fecal apparent total N-nitroso compounds (ATNC) and the formation of nitroso-compound-specific DNA adducts. Red meat is particularly rich in heme and heme has also been found to promote the formation of ATNC. To investigate the underlying mechanism of ATNC formation, fecal and ileal samples of volunteers fed a high red meat or a vegetarian diet were analyzed for nitrosyl iron, nitrosothiols, and heme. To simulate the processes in the stomach, food homogenates and hemoglobin were incubated under simulated gastric conditions. Nitrosyl iron and nitrosothiols were significantly (p < 0.0001) increased in ileal and fecal samples after a high red meat diet compared with a vegetarian diet; significantly more nitrosyl iron than nitrosothiols was detectable in ileal (p < 0.0001) and fecal (p < 0.001) samples. The strong correlation between fecal nitrosyl iron and heme (0.776; p < 0.0001) suggested that nitrosyl heme is the main source of nitrosyl iron, and ESR confirmed the presence of nitrosyl heme in fecal samples after a high red meat diet. Under simulated gastric conditions, mainly nitrosothiols were formed, suggesting that acid-catalyzed thionitrosation is the initial step in the endogenous formation of nitroso compounds. Nitrosyl heme and other nitroso compounds can then form under the alkaline and reductive conditions of the small and large bowel.
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“This might partly explain why patients with achlorhydria and non-vegetarians eating large amounts of cured meats are at risk of developing gastric cancer [137,138,139,140,141,142].”
From NO-Rich Diet for Lifestyle-Related Diseases (2015) · cites this paper as [140]
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Background
Metadata
- Authors
- Kuhnle, G. G. C., Story, G. W., Reda, T., Mani, A. R., Moore, K. P., Lunn, J. C., & Bingham, S. A.
- Affiliations
- MRC Mitochondrial Biology Unit (GB)
- The Royal Free Hospital (GB)
- Corresponding author
- Bingham, Sheila A.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 43
- Issue
- 7
- Pages
- 1040-1047
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2079577516
- Cited by
- 146
- References
- 59
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 27 · 2023: 7 · 2022: 6 · 2021: 5 · 2020: 6 · 2019: 10 · 2018: 7 · 2017: 7 · 2016: 4 · 2015: 9 · 2014: 7 · 2013: 7 · 2012: 4
- FWCI
- 10.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Food Standards Agency
- Medical Research Council
- Topics
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Meat and Animal Product Quality
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Keywords
- nitroso compounds, endogenous nitrosation, red meat, processed meat, heme, S-nitrosothiols, colorectal cancer, DNA adducts, simulated gastric conditions, hemoglobin, vegetarian diet, gastrointestinal tract
- MeSH terms
- Apoproteins, Diet, Electron Spin Resonance Spectroscopy, Feces, Gastric Mucosa, Heme, Hemoglobins, Humans, Ileum, Iron, Kinetics, Meat, Nitroso Compounds, Serum Albumin, Bovine, Diet, Vegetarian, S-Nitrosothiols, Gastrointestinal Tract
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