Diet-induced endogenous formation of nitroso compounds in the GI tract

Kuhnle, Gunter G.C.; Story, Giles W.; Reda, Torsten; Mani, Ali R.; Moore, Kevin P.; Lunn, Joanne C.; Bingham, Sheila A.

doi:10.1016/j.freeradbiomed.2007.03.011

Cited by 146Meat and Animal Product QualityNutritional Studies and DietAntioxidant Activity and Oxidative Stress

Diet-induced endogenous formation of nitroso compounds in the GI tract

Kuhnle, Gunter G.C., Story, Giles W., Reda, Torsten, Mani, Ali R., Moore, Kevin P., Lunn, Joanne C., Bingham, Sheila A.·2007·Free Radical Biology and Medicine

DOI 10.1016/j.freeradbiomed.2007.03.011

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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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The chemistry of nitrite in the stomach might partly explain why patients with achlorhydria and non-vegetarians eating large amounts of cured meats are at risk of developing gastric cancer.
“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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Demeyer, D. I., Honikel, K. O., & SMET, S. D. (2008) · Meat Science · doi:10.1016/j.meatsci.2008.06.003 · Cited by 107 · see citing works
“The formation of N-nitroso compounds (NOC) under influence of haem as a possible explanation was further substantiated by Kuhnle and Bingham (2007) and Kuhnle et al. (2007).”
Anthocyanins, non-anthocyanin phenolics, tocopherols and antioxidant capacity of açaí juice (Euterpe oleracea) as affected by high pressure processing and thermal pasteurization
da Silveira, T. F. F., Cristianini, N., Kuhnle, G., Ribeiro, A. B., Filho, J. T., & Godoy, H. T. (2019) · Innovative Food Science & Emerging Technologies · doi:10.1016/j.ifset.2019.05.001 · Cited by 97 · see citing works
Dissecting the mechanisms and molecules underlying the potential carcinogenicity of red and processed meat in colorectal cancer (CRC): an overview on the current state of knowledge
Cascella, M., Bimonte, S., Barbieri, A., Vecchio, V. D., Caliendo, D., Schiavone, V., Fusco, R., Granata, V., Arra, C., & Cuomo, A. (2018) · Infectious Agents and Cancer · doi:10.1186/s13027-018-0174-9 · Cited by 96 · see citing works
“[70], the presence of nitrosyl heme, which is formed by a nitrosylation or nitrosation in ileum and in faeces, might promote the formation of extremely reactive alkylating agents like diazoacetate.”
Background
A prospective study of meat, cooking methods, meat mutagens, heme iron, and lung cancer risks
Tasevska, N., Sinha, R. R., Kipnis, V., Subar, A. F., Leitzmann, M. F., Hollenbeck, A. R., Caporaso, N. E., Schatzkin, A. G., & Cross, A. J. (2009) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.2008.27272 · Cited by 95 · see citing works
NO-Rich Diet for Lifestyle-Related Diseases
Kobayashi, J., Ohtake, K., & Uchida, H. (2015) · Nutrients · doi:10.3390/nu7064911 · Cited by 94 · see citing works
Metabolism of nitro drugs metronidazole and nitazoxanide in Giardia lamblia: characterization of a novel nitroreductase (GlNR2)
Müller, J., Schildknecht, P., & Müller, N. (2013) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkt106 · Cited by 88 · see citing works
Dietary meat, endogenous nitrosation and colorectal cancer
Kuhnle, G., & Bingham, S. A. (2007) · Biochemical Society Transactions · doi:10.1042/bst0351355 · Cited by 83 · see citing works
Radical Mechanisms in Nitrosamine- and Nitrosamide-Induced Whole-Genome Gene Expression Modulations in Caco-2 Cells
Hebels, D. G. A. J., Briedé, J. J., Khampang, R., Kleinjans, J. C. S., & de Kok, T. M. C. M. (2010) · Toxicological Sciences · doi:10.1093/toxsci/kfq121 · Cited by 74 · see citing works
“NOCs have been found in the environment and certain types of food, such as beer, fish, and nitrite-preserved meat (Tricker and Preussmann, 1991), but can also be formed endogenously by nitrosation of dietary precursors, a process that occurs predominantly in the gastrointestinal tract (Kuhnle et al., 2007; Mirvish, 19…”
Background
Iron in red meat–friend or foe
Czerwonka, M., & Tokarz, A. (2016) · Meat Science · doi:10.1016/j.meatsci.2016.09.012 · Cited by 80 · see citing works
Recommendation-based dietary indexes and risk of colorectal cancer in the Nurses’ Health Study and Health Professionals Follow-up Study
Petimar, J., Smith‐Warner, S. A., Fung, T. T., ROSNER, B. A., Chan, A. T., Hu, F. B., Giovannucci, E. L., & Tabung, F. K. (2018) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqy171 · Cited by 74 · see citing works
Probiotic lactic acid bacteria detoxify N-nitrosodimethylamine
Nowak, A., Kuberski, S., & Libudzisz, Z. (2014) · Food Additives & Contaminants Part A · doi:10.1080/19440049.2014.943304 · Cited by 61 · see citing works
“The major effect of nitrosamines is alkylation of DNA and the induction of GC-AT transitions in genes (Kuhnle et al. 2007; Dubrow et al. 2010).”
Background
Red meat and colon cancer: A review of mechanistic evidence for heme in the context of risk assessment methodology
Kruger, C. L., & Zhou, Y. (2018) · Food and Chemical Toxicology · doi:10.1016/j.fct.2018.04.048 · Cited by 61 · see citing works
Dietary, lifestyle and clinicopathological factors associated with APC mutations and promoter methylation in colorectal cancers from the EPIC‐Norfolk study
Gay, L. J., Mitrou, P. N., Keen, J., Bowman, R., Naguib, A., Cooke, J. C., Kuhnle, G., Burns, P. A., Luben, R., Lentjes, M. A. H., et al. (2012) · The Journal of Pathology · doi:10.1002/path.4085 · Cited by 58 · see citing works
Molecular Signatures of N-nitroso Compounds in Caco-2 Cells: Implications for Colon Carcinogenesis
Hebels, D. G. A. J., Jennen, D. G. J., Kleinjans, J. C. S., & de Kok, T. M. C. M. (2009) · Toxicological Sciences · doi:10.1093/toxsci/kfp035 · Cited by 56 · see citing works
“NOC can also be formed endogenously by nitrosation of dietary precursors, a process that occurs predominantly in the gastrointestinal tract (Kuhnle et al., 2007; Mirvish, 1995).”
BackgroundInfluential
Red meat intake-induced increases in fecal water genotoxicity correlate with pro-carcinogenic gene expression changes in the human colon
Hebels, D. G. A. J., Sveje, K. M., de Kok, M. C., van Herwijnen, M. H. M., Kuhnle, G., Engels, L. G. J. B., Vleugels-Simon, C. B. E. M., Mares, W. G. N., Pierik, M. J., Masclee, A., et al. (2011) · Food and Chemical Toxicology · doi:10.1016/j.fct.2011.10.038 · Cited by 52 · see citing works
The relationship of red meat with cancer: Effects of thermal processing and related physiological mechanisms
Chiang, V. S., & Quek, S. Y. (2015) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2014.967833 · Cited by 52 · see citing works
“No studies could be identified to relate inflammation with NOCs but heme iron, described earlier as a promoter for endogenous NOC production, was found to induce inflammation in mice (Wagener et al., 2001), though this was the only study identified to date.”
BackgroundResultInfluential
Substituting meat for mycoprotein reduces genotoxicity and increases the abundance of beneficial microbes in the gut: Mycomeat, a randomised crossover control trial
Farsi, D. N., Lara, J., Koutsidis, G., Nelson, A., Finnigan, T. J. A., Cheung, W., Muñoz-Muñoz, J., & Commane, D. M. (2023) · European Journal of Nutrition · doi:10.1007/s00394-023-03088-x · Cited by 51 · see citing works
“Faecal nitrates, nitrites and total NOC were determined using chemiluminescence as described previously [24].”
Method
Red Wine and Pomegranate Extracts Suppress Cured Meat Promotion of Colonic Mucin-Depleted Foci in Carcinogen-Induced Rats
Bastide, N. M., Naud, N., Nassy, G., Vendeuvre, J., Taché, S., Guéraud, F., Hobbs, D. A., Kuhnle, G., Corpet, D. E., & Pierre, F. H. F. (2017) · Nutrition and Cancer · doi:10.1080/01635581.2017.1263745 · Cited by 44 · see citing works
“ATNC Analysis ATNC were analyzed using a modification of the method previously used (37), using a CLD88 Exhalyzer (Ecomedics, Duernten, Switzerland).”
BackgroundMethod
Consumption of Red/Processed Meat and Colorectal Carcinoma: Possible Mechanisms Underlying the Significant Association
Hammerling, U., Laurila, J. B., Grafström, R., & Ilbäck, N. (2015) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2014.972498 · Cited by 47 · see citing works
“A series of reports consistently show higher intestinal NOC levels following high meat diets, compared with those of poultry or fish (Hughes et al., 2001; Bingham et al., 2002; Cross et al., 2003; Kuhnle et al., 2007; Joosen et al., 2009).”
Background
The cancer risk related to meat and meat products
Johnson, I. T. (2016) · British Medical Bulletin · doi:10.1093/bmb/ldw051 · Cited by 47 · see citing works
“Apart from the secondary bile acids previously mentioned, meat consumption has also been implicated in the production of ammonia and other potentially mutagenic protein derivatives and of endogenous NOCs, all derived from microbial metabolism of food residues in the alimentary tract.(28) Amines and amides are formed i…”
Background
Dietary intake of heme iron and risk of gastric cancer in the European prospective investigation into cancer and nutrition study
Jakszyn, P. G., Agudo, A., Luján‐Barroso, L., Bueno-de-Mesquita, H. B., Jenab, M., Navarro, C., Palli, D., Boeing, H., Manjer, J., Numans, M. E., et al. (2011) · International Journal of Cancer · doi:10.1002/ijc.26263 · Cited by 45 · see citing works
“In fact, red meat is rich in heme iron, which is the likely responsible agent for the endogenous NOCs formation.(8,9) Our results from the EURGAST study(5) have shown a significant positive association between the estimated endogenous NOC production (from iron in meat) and risk of noncardia GC.”
Background
Chemical hazards in foods of animal origin
Smulders, F. J. M., Rietjens, I. M. C. M., & Rose, M. (2018) · Wageningen Academic Publishers eBooks · doi:10.3920/978-90-8686-877-3 · Cited by 48 · see citing works
Consumption of Nitrate-Rich Beetroot Juice with or without Vitamin C Supplementation Increases the Excretion of Urinary Nitrate, Nitrite, and N-nitroso Compounds in Humans
Berends, J. E., van den Berg, L. M. M., Guggeis, M. A., Henckens, N. F. T., Hossein, I. J., de Joode, M. E. J. R., Zamani, H., van Pelt, K. A. A. J., Beelen, N. A., Kuhnle, G., et al. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20092277 · Cited by 45 · see citing works
“To analyze nitrate and nitrite concentrations in urine, chemiluminescence was used [33].”
Method
Beyond the Cortical Column: Abundance and Physiology of Horizontal Connections Imply a Strong Role for Inputs from the Surround
Boucsein, C., Nawrot, M. P., Schnepel, P., & Aertsen, A. (2011) · Frontiers in Neuroscience · doi:10.3389/fnins.2011.00031 · Cited by 44 · see citing works
White açaí juice (Euterpe oleracea): Phenolic composition by LC-ESI-MS/MS, antioxidant capacity and inhibition effect on the formation of colorectal cancer related compounds
da Silveira, T. F. F., de Souza, T. C. L., Carvalho, A. V., Ribeiro, A. B., Kuhnle, G., & Godoy, H. T. (2017) · Journal of Functional Foods · doi:10.1016/j.jff.2017.07.001 · Cited by 43 · see citing works
Impact of DNA repair on the dose-response of colorectal cancer formation induced by dietary carcinogens
Fahrer, J., & Kaina, B. (2016) · Food and Chemical Toxicology · doi:10.1016/j.fct.2016.09.029 · Cited by 41 · see citing works
No effect of meat, meat cooking preferences, meat mutagens or heme iron on lung cancer risk in the prostate, lung, colorectal and ovarian cancer screening trial
Tasevska, N., Cross, A. J., Dodd, K. W., Ziegler, R. G., Caporaso, N. E., & Sinha, R. R. (2010) · International Journal of Cancer · doi:10.1002/ijc.25327 · Cited by 39 · see citing works
“Heme iron can act as a pro-oxidant and can catalyze lipid peroxidation and cause DNA damage in tissue,(14,15) while it was also shown to induce NOCs endogenous formation.(11,12) Fat content of meat, specifically, may also play a role, although no plausible mechanisms that relate to lung carcinogenesis have been sugges…”
Background
Physiological aspects of nitro drug resistance in Giardia lamblia
Müller, J., Hemphill, A. F., & Müller, N. (2018) · International Journal for Parasitology Drugs and Drug Resistance · doi:10.1016/j.ijpddr.2018.04.008 · Cited by 38 · see citing works
“…history of this protozoan parasite, which must face dietary shifts of its omnivorous hosts ranging from a carbohydrate-rich to a red meat-rich diet, resulting in an accumulation of nitrosamines and other reactive nitrogen species (Hughes et al., 2001; Kuhnle et al., 2007; Joosen et al., 2009).”
Background
Iron-catalysed chemistry in the gastrointestinal tract: Mechanisms, kinetics and consequences. A review
Bechaux, J., Pomélie, D. D. L., Théron, L., Santé-Lhoutellier, V., & Gatellier, P. (2018) · Food Chemistry · doi:10.1016/j.foodchem.2018.06.018 · Cited by 37 · see citing works
Intestinal Formation of N-Nitroso Compounds in the Pig Cecum Model
Engemann, A., Focke, C., & Humpf, H. (2013) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf305040e · Cited by 37 · see citing works
Dietary exposure to meat-related carcinogenic substances: is there a way to estimate the risk?
Trafiałek, J., & Kolanowski, W. (2014) · International Journal of Food Sciences and Nutrition · doi:10.3109/09637486.2014.917146 · Cited by 35 · see citing works
“gastrointestinal tract for acid catalyzed N-nitrosation (Kuhnle et al., 2007; Loh et al., 2011).”
Background
N-nitroso compound exposure-associated transcriptomic profiles are indicative of an increased risk for colorectal cancer
Hebels, D. G. A. J., Sveje, K. M., de Kok, M. C., van Herwijnen, M. H. M., Kuhnle, G., Engels, L. G. J. B., Vleugels-Simon, C. B. E. M., Mares, W. G. N., Pierik, M. J., Masclee, A., et al. (2011) · Cancer Letters · doi:10.1016/j.canlet.2011.05.007 · Cited by 34 · see citing works
“Apparent total nitroso compounds (ATNC) were analyzed in feces by thermal energy analysis as described previously [18], using an Ecomedics CLD88 Exhalyzer (Ecomedics, Duernten, Switzerland).”
Method
Current study of pathogenetic mechanisms and therapeutics of chronic atrophic gastritis: a comprehensive review
Kuang, W., Xu, J., Xu, F., Huang, W., Majid, M., Shi, H., Yuan, X., Ruan, Y., & Hu, X. (2024) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2024.1513426 · Cited by 33 · see citing works
O6‐carboxymethylguanine DNA adduct formation and lipid peroxidation upon in vitro gastrointestinal digestion of haem‐rich meat
Bussche, J. V., Hemeryck, L., HECKE, T. V., Kuhnle, G., Pasmans, F., Moore, S. A., de Wiele, T. V., SMET, S. D., & Vanhaecke, L. (2014) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201400078 · Cited by 33 · see citing works
Red Meat-Derived Nitroso Compounds, Lipid Peroxidation Products and Colorectal Cancer
Steinberg, P. (2019) · Foods · doi:10.3390/foods8070252 · Cited by 33 · see citing works
“Under alkaline conditions, nitric oxide may in part react with heme molecules [22], so that the nitrosyl heme is formed [20].”
Replacement of Nitrite in Meat Products by Natural Bioactive Compounds Results in Reduced Exposure to N‐Nitroso Compounds: The PHYTOME Project
Breda, S. G. J. V., Mathijs, K., Pieters, H., Sági‐Kiss, V., Kuhnle, G., Georgiadis, P., Saccani, G., Parolari, G., Virgili, R., Sinha, R. R., et al. (2021) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202001214 · Cited by 31 · see citing works
Reformulation of processed meat to attenuate potential harmful effects in the gastrointestinal tract – A review of current knowledge and evidence of health prospects
Thøgersen, R., & Bertram, H. C. (2020) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2020.12.015 · Cited by 30 · see citing works
Plant-Based Diet and Risk of Iron-deficiency Anemia. A Review of the Current Evidence and Implications for Preventive Strategies
López‐Moreno, M., Castillo‐García, A., Roldán‐Ruiz, A., Viña, I., & Bertotti, G. (2025) · Current Nutrition Reports · doi:10.1007/s13668-025-00671-y · Cited by 29 · see citing works
“Similarly, heme iron acts as a catalyst for the formation of nitrosamines (NOCs), which are recognised carcinogens according to the IARC [69].”
Inulin-fortification of a processed meat product attenuates formation of nitroso compounds in the gut of healthy rats
Thøgersen, R., Gray, N., Kuhnle, G., HECKE, T. V., SMET, S. D., Young, J. F., Sundekilde, U. K., Hansen, A. K., & Bertram, H. C. (2019) · Food Chemistry · doi:10.1016/j.foodchem.2019.125339 · Cited by 29 · see citing works
A study of the bioactive potential of seven neglected and underutilized leaves consumed in Brazil
de Souza, T. C. L., da Silveira, T. F. F., Rodrigues, M. I., Ruiz, A. L. T. G., Neves, D. A., Duarte, M. C. T., Cunha, E. C. E., Kuhnle, G., Ribeiro, A. B., & Godoy, H. T. (2021) · Food Chemistry · doi:10.1016/j.foodchem.2021.130350 · Cited by 29 · see citing works
The dual function of nitrite under stomach conditions is modulated by reducing compounds
Volk, J., Gorelik, S., Granit, R., Kohen, R., & Kanner, J. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.04.012 · Cited by 29 · see citing works
Gut microbiota can utilize prebiotic birch glucuronoxylan in production of short-chain fatty acids in rats
Kynkäänniemi, E., Lahtinen, M. H., Jian, C., Salonen, A., Hatanpää, T., Mikkonen, K. S., & Pajari, A. (2022) · Food & Function · doi:10.1039/d1fo03922a · Cited by 26 · see citing works
Effect of dietary meat and fish on endogenous nitrosation, inflammation and genotoxicity of faecal water
Joosen, A. M. C. P., Lecommandeur, E., Kuhnle, G., Aspinall, S. M., Kap, L., & Rodwell, S. A. (2010) · Mutagenesis · doi:10.1093/mutage/gep070 · Cited by 26 · see citing works
“This confirms the important contribution of haem to endogenous nitrosation (18).”
BackgroundMethodInfluential
Heme-Induced Biomarkers Associated with Red Meat Promotion of colon Cancer Are Not Modulated by the Intake of Nitrite
Chenni, F. Z., Taché, S., Naud, N., Guéraud, F., Hobbs, D. A., Kunhle, G. C. G., Pierre, F. H. F., & Corpet, D. E. (2013) · Nutrition and Cancer · doi:10.1080/01635581.2013.749291 · Cited by 23 · see citing works
“Nitrosyl heme is the main source of iron nitrosyl (44), which is consistent with the strong NO-scavenging activity of hemoglobin (47).”
Background
Relationships between gut microbiota, red meat consumption and colorectal cancer.
Diakité, M., Diakité, B., Koné, A., Balam, S., Fofana, D., Diallo, D., Kassogué, Y., Traoré, C. B., Kamaté, B., Ba, D. M., et al. (2022) · PubMed · Cited by 24 · see citing works
Effects of sodium nitrite reduction, removal or replacement on cured and cooked meat for microbiological growth, food safety, colon ecosystem, and colorectal carcinogenesis in Fischer 344 rats
Guéraud, F., Buisson, C., Promeyrat, A., Naud, N., Fouché, E., Bézirard, V., Dupuy, J., Plaisancié, P., Héliès‐Toussaint, C., Trouilh, L., et al. (2023) · npj Science of Food · doi:10.1038/s41538-023-00228-9 · Cited by 23 · see citing works
Epidemiology, Molecular Mechanisms, and Clinical Trials: an Update on Research on the Association Between Red Meat Consumption and Colorectal Cancer
Kossenas, K., & Constantinou, C. (2021) · Current Nutrition Reports · doi:10.1007/s13668-021-00377-x · Cited by 23 · see citing works
Dietary nitrite induces nitrosation of the gastric mucosa: the protective action of the mucus and the modulatory effect of red wine
Pereira, C., Barbosa, R. M., & Laranjinha, J. A. N. (2015) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2014.12.004 · Cited by 23 · see citing works
“6 × 10(2) M−2 s−1) [23,24] under similar experimental conditions [21] in particular at lower pH [23,25] and in presence of bicarbonate [26], such as found in the gastric environment.”
Using a dynamic artificial digestive system to investigate heme iron nitrosylation during gastro-intestinal transit
Pomélie, D. D. L., Santé-Lhoutellier, V., Sayd, T., Théron, L., & Gatellier, P. (2019) · Food Chemistry · doi:10.1016/j.foodchem.2018.12.094 · Cited by 23 · see citing works
Kiwifruit as a Modulator of DNA Damage and DNA Repair
Collins, A. R. (2013) · Advances in food and nutrition research · doi:10.1016/b978-0-12-394294-4.00016-x · Cited by 22 · see citing works
Recent Perspectives on the Relations between Fecal Mutagenicity, Genotoxicity, and Diet
Gratz, S. W., Wallace, R. J., & El-Nezami, H. S. (2011) · Frontiers in Pharmacology · doi:10.3389/fphar.2011.00004 · Cited by 20 · see citing works
“Different methods are used to illustrate the proportion of DNA remaining in the Comet Head (i.e., undamaged DNA) and in the Comet tail (i.e., excretion of less mutagenic stools in six volunteers compared to a high risk mixed diet (Kuhnlein et al., 1983).”
Diet Composition Is Associated with Endogenous Formation of N-Nitroso Compounds in Obese Men
Holtrop, G., Johnstone, A. M., Fyfe, C., & Gratz, S. W. (2012) · Journal of Nutrition · doi:10.3945/jn.112.158824 · Cited by 20 · see citing works
The effects of substituting red and processed meat for mycoprotein on biomarkers of cardiovascular risk in healthy volunteers: an analysis of secondary endpoints from Mycomeat
Farsi, D. N., Lara, J., Finnigan, T. J. A., Cheung, W., Muñoz-Muñoz, J., & Commane, D. M. (2023) · European Journal of Nutrition · doi:10.1007/s00394-023-03238-1 · Cited by 22 · see citing works
“Urinary nitrates and nitrites were determined using chemiluminescence as described previously [31].”
Method
Inulin and milk mineral fortification of a pork sausage exhibits distinct effects on the microbiome and biochemical activity in the gut of healthy rats
Thøgersen, R., Castro-Mejía, J. L., Sundekilde, U. K., Hansen, L. H., Gray, N., Kuhnle, G., Jørgensen, N. R., Hansen, A. K., Nielsen, D. S., & Bertram, H. C. (2020) · Food Chemistry · doi:10.1016/j.foodchem.2020.127291 · Cited by 17 · see citing works
Dietary Nitrosamines from Processed Meat Intake as Drivers of the Fecal Excretion of Nitrosocompounds
Ruiz-Saavedra, S., Pietilä, T. K., Zapico, A., Reyes‐Gavilán, C. G. D. L., Pajari, A., & González, S. (2024) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.4c05751 · Cited by 14 · see citing works
“28,29 Unless otherwise stated, the chemicals were obtained from Sigma-Aldrich (Merck Life Science).”
Method
Induction of Colonic Aberrant Crypts in Mice by Feeding Apparent N-Nitroso Compounds Derived From Hot Dogs
Davis, M. E., Lisowyj, M. P., Zhou, L., Wisecarver, J. L., Gulizia, J. M., Shostrom, V., Naud, N., Corpet, D. E., & Mirvish, S. S. (2012) · Nutrition and Cancer · doi:10.1080/01635581.2012.650777 · Cited by 14 · see citing works
“Each set of results included thos e f r total ANC and for ANC after addition of mercuric chloride (HgCl2), a test for R SNO, or of potassium ferricyanide [K3Fe(CN)6], a test for nitrosyl iron compounds [RF eNO] (17).”
Method
The colon carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is actively secreted in the distal colon of the rat: an integrated view on the role of PhIP transport and metabolism in PhIP-induced colon carcinogenesis
Nicken, P., Schröder, B., von Keutz, A., Breves, G., & Steinberg, P. (2013) · Archives of Toxicology · doi:10.1007/s00204-012-1006-0 · Cited by 14 · see citing works
“…(e.g. endogenously formed N-nitroso compounds) (Bingham et al. 1996; Hughes et al. 2001; Bingham et al. 2002; Cross et al. 2003; Lewin et al. 2006; Kuhnle et al. 2007) and other risk factors (ethanol, tobacco and/or obesity among others) are responsible for the high colorectal cancer incidence…”
Background
In vitro digestion of nitrite and nitrate preserved fermented sausages – New understandings of nitroso-compounds’ chemical reactivity in the digestive tract
Keuleyan, E., Bonifacie, A., Sayd, T., Duval, A., Aubry, L., Bourillon, S., Gatellier, P., Promeyrat, A., Nassy, G., Scislowski, V., et al. (2022) · Food Chemistry X · doi:10.1016/j.fochx.2022.100474 · Cited by 13 · see citing works
“Those adducts generally promote mutagenesis, and through multiple reactions, may trigger carcinogenesis (Kuhnle et al., 2007; Van Hecke, Vanden Bussche, Vanhaecke, Vossen, Van Camp, & De Smet, 2014).”
Background
Nitrosative deamination of 2′-deoxyguanosine and DNA by nitrite, and antinitrosating activity of β-carboline alkaloids and antioxidants
Herraiz, T., & Galisteo, J. (2017) · Food and Chemical Toxicology · doi:10.1016/j.fct.2017.12.042 · Cited by 13 · see citing works
Synthesis and in vitro characterization of the genotoxic, mutagenic and cell-transforming potential of nitrosylated heme
Kostka, T., Fohrer, J., Guigas, C., Briviba, K., Seiwert, N., Fahrer, J., Steinberg, P., & Empl, M. T. (2020) · Archives of Toxicology · doi:10.1007/s00204-020-02846-8 · Cited by 12 · see citing works
Chemical effects of nitrite reduction during digestion of cured cooked and recooked meat on nitrosation, nitrosylation and oxidation
Bonifacie, A., Aubry, L., Sayd, T., Bourillon, S., Duval, A., Kombolo, M., Nassy, G., Promeyrat, A., Santé-Lhoutellier, V., & Théron, L. (2024) · Food Research International · doi:10.1016/j.foodres.2024.114969 · Cited by 11 · see citing works
El consumo de nitrato y su potencial efecto benéfico sobre la salud cardiovascular
Brayan Moreno, C., Karen Soto, O., & González, D. R. (2015) · Revista chilena de nutrición · doi:10.4067/s0717-75182015000200013 · Cited by 11 · see citing works
Detection of N ‐nitroso‐bile acids at 285 nm in reverse‐phase HPLC
Araki, Y., Mukaisyo, K.-I., Sugihara, H., Fujiyama, Y., & Hattori, T. (2008) · Journal of Separation Science · doi:10.1002/jssc.200800230 · Cited by 10 · see citing works
Iron and Cancer
Connor, J. R., & Lee, S. Y. (2010) · Humana Press eBooks · doi:10.1007/978-1-60761-627-6_21 · Cited by 9 · see citing works
A comparative analysis of heme vs non-heme iron administration: a systematic review and meta-analysis of randomized controlled trials
Ruelas, M. G., Alvarado‐Gamarra, G., Aramburú, A., Dolores-Maldonado, G. K., Rodríguez, K. C., Rojas-Limache, G., Díaz-Parra, C. D. P., & Lanata, C. F. (2024) · European Journal of Nutrition · doi:10.1007/s00394-024-03564-y · Cited by 9 · see citing works
Urinary Excretion of N-Nitroso Compounds in Rats Fed Sodium Nitrite and/or Hot Dogs
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Untitled work
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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.
ORCID: Kuhnle, Gunter G.C.
Story, Giles W.
Mani, Ali R.
Venue: Free Radical Biology and Medicine
Publisher: Elsevier BV
Published: 2007-10
Volume: 43
Issue: 7
Pages: 1040-1047
ISSN: 0891-5849 (ISSN-L)
DOI: 10.1016/j.freeradbiomed.2007.03.011
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
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 › 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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Diet-induced endogenous formation of nitroso compounds in the GI tract

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