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Gunter G C Kuhnle - One of the best experts on this subject based on the ideXlab platform.

  • red wine and pomegranate extracts suppress cured meat promotion of colonic mucin depleted foci in carcinogen induced rats
    Nutrition and Cancer, 2017
    Co-Authors: Nadia M Bastide, Gunter G C Kuhnle, Nathalie Naud, Gilles Nassy, Jeanluc Vendeuvre, Sylviane Tache, Francoise Gueraud, Ditte A Hobbs, Denis E Corpet, Fabrice Pierre
    Abstract:

    Processed meat intake is carcinogenic to humans. We have shown that intake of a workshop-made cured meat with erythorbate promotes colon carcinogenesis in rats. We speculated that polyphenols could inhibit this effect by limitation of endogenous lipid peroxidation and nitrosation. Polyphenol-rich plant extracts were added to the workshop-made cured meat and given for 14 days to rats and 100 days to azoxymethane-induced rats to evaluate the inhibition of preneoplastic lesions. Colons of 100-d study were scored for precancerous lesions (mucin-depleted foci, MDF), and biochemical end points of peroxidation and nitrosation were measured in urinary and fecal samples. In comparison with cured meat-fed rats, dried red wine, pomegranate extract, a-tocopherol added at one dose to cured meat and withdrawal of erythorbate significantly decreased the number of MDF per colon (but white grape and rosemary extracts did not). This protection was associated with the full suppression of fecal excretion of nitrosyl iron, suggesting that this Nitroso Compound might be a promoter of carcinogenesis. At optimized concentrations, the incorporation of these plant extracts in cured meat might reduce the risk of colorectal cancer associated with processed meat consumption.

  • o6 carboxymethylguanine dna adduct formation and lipid peroxidation upon in vitro gastrointestinal digestion of haem rich meat
    Molecular Nutrition & Food Research, 2014
    Co-Authors: Julie Vanden Bussche, Thomas Van Hecke, Stefaan De Smet, Lieselot Hemeryck, Gunter G C Kuhnle, Frank Pasmans, Sharon A Moore, Tom Van De Wiele, Lynn Vanhaecke
    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.

  • n Nitroso Compound exposure associated transcriptomic profiles are indicative of an increased risk for colorectal cancer
    Cancer Letters, 2011
    Co-Authors: Dennie G A J Hebels, Gunter G C Kuhnle, Kirstine M Sveje, Marloes C De Kok, Marcel H M Van Herwijnen, L G J B Engels, Carla B Vleugelssimon, Wout G N Mares, Marieke Pierik, A A M Masclee
    Abstract:

    Endogenous formation of N-Nitroso Compounds (NOCs), which are known animal carcinogens, could contribute to human carcinogenesis but definitive evidence is still lacking. To investigate the relevance of NOCs in human colorectal cancer (CRC) development, we analyzed whole genome gene expression modifications in human colon biopsies in relation to fecal NOC exposure. We had a particular interest in patients suffering from intestinal inflammation as this may stimulate endogenous NOC formation, and consequently predispose to CRC risk. Inflammatory bowel disease (IBD) patients diagnosed with ulcerative colitis and irritable bowel syndrome patients without inflammation, serving as controls, were therefore recruited. Fecal NOC were demonstrated in the majority of subjects. By associating gene expression levels of all subjects to fecal NOC levels, we identified a NOC exposure-associated transcriptomic response that suggests that physiological NOC concentrations may potentially induce genotoxic responses and chromatin modifications in human colon tissue, both of which are linked to carcinogenicity. In a network analysis, chromatin modifications were linked to 11 significantly modulated histone genes, pointing towards a possible epigenetic mechanism that may be relevant in comprehending NOC-induced carcinogenesis. In addition, pro-inflammatory transcriptomic modifications were identified in visually non-inflamed regions of the IBD colon. However, fecal NOC levels were slightly but not significantly increased in IBD patients, suggesting that inflammation did not strongly stimulate NOC formation. We conclude that NOC exposure is associated with gene expression modifications in the human colon that may suggest a potential role of these Compounds in CRC development.

  • dietary meat endogenous nitrosation and colorectal cancer
    Biochemical Society Transactions, 2007
    Co-Authors: Gunter G C Kuhnle, Sheila Bingham
    Abstract:

    Colorectal cancer is the third most common cancer in developed countries such as the U.K., but incidence rates around the world vary approx. 20-fold. Diet is thought to be a key factor determining risk: red and processed meat, but not white meat or fish, are associated with an increased risk of colorectal cancer. The endogenous formation of N-Nitroso Compounds is a possible explanation because red and processed meat, but not white meat or fish, cause a dose-dependent increase in faecal ATNCs (apparent total N-Nitroso Compounds) and the formation of Nitroso-Compound-specific DNA adducts in humans. Red meat is particularly rich in haem which has been found to promote the endogenous formation of ATNC. Nitrosyl haem and Nitroso thiols have been identified as major constituents of both faecal and ileal ATNC with a significant increase in the formation of these Compounds following a diet rich in red meat. In vitro incubations show that, under simulated gastric conditions, Nitroso thiols are the main species of Nitroso Compound formed, suggesting that acid-catalysed thionitrosation is the initial step in the endogenous formation of Nitroso Compounds. Nitrosyl haem and other Nitroso Compounds can then form under the alkaline and reductive conditions of the small and large bowel.

Sidney S Mirvish - One of the best experts on this subject based on the ideXlab platform.

  • abstract 3446 induction of colonic aberrant crypts in mice by an apparent n Nitroso Compound fraction derived from hot dogs
    Cancer Research, 2010
    Co-Authors: Michael E Davis, Michal P Lisowyj, James L Wisecarver, James M Gulizia, Sidney S Mirvish
    Abstract:

    Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Introduction: Nitrite-preserved meat products, e.g., hot dogs, may be a cause of colon cancer. This may occur because such products contain a possibly carcinogenic fraction called “total apparent N-Nitroso Compounds” (ANC). Feeding such products to humans and mice increased the fecal excretion of ANC. We tested here whether hot-dog-derived ANC could induce colonic aberrant crypts (ABC), a precursor lesion for colon cancer, in mice. Methods: We purified the ANC precursor (ANCP) fraction of commercial hot hogs by adsorption-desorption on silica gel and cation exchange resin, and treated the ANCP with nitrite to convert them to ANC. As a positive control group, adult female A/J mice were given 1 or 3 i.p. injections of 5 mg/kg of azoxymethane (AOM) [Experiment (Exp.) 1]. In Exps. 2 and 3, similar mice were continuously fed the purified hot dog ANC (initial dose, 100 nmol/g diet) in a high-fat or “high-fat stress” diet. In Exp. 2 the ANC dose initially dropped sharply, probably because the ANCP was unstable on thawing, but later in Exp 2 and throughout Exp 3 the ANCP level was stable and was maintained at 100 nmol/g diet. The mice were killed after 8 (for AOM tests) or 24-34 (for ANC tests) weeks of treatment. Feces of the ANC-treated mice contained up to 225 nmol ANC/g, indicating that the ANC reached the colon. The distal 2 cm of each colon was stained with methylne blue, the mucosal surfaces were scanned at 400 x magnification, and ABC were identified and counted. Results: Mean numbers of ANC/colon for 1 and 3 AOM injections, AOM controls, ANC (Exp 2), ANC (Exp. 3) and ANC controls were 28, 76, 14, 20, 14 and 5-8. Standard deviations were <50% of mean values. The effect of ANC was significant by the rank order test (P < 0.01) for both Exps. 2 and 3. Potency of ABC induction per mole ANC was 1.7% (Exp. 2) and 0.4% (Exp. 3) of that for AOM in Exp. 1. In Exp. 3 we noted that the ABC occurred as foci with 1-4 ABC/focus and a mean of 6.8 foci/colon. ANC treatment did not affect the number of foci. Conclusions: Hot-dog-derived ANC induced a significant number of ABC in the mouse colon, but the effect was relatively weak. These results provide a direct link between ANC in a nitrite-preserved meat product and effects in the colon. Partly supported by NIH grant RO1 CA-143460-01. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3446.

  • further studies on apparent total n Nitroso Compound excretion in mouse feces
    Cancer Epidemiology and Prevention Biomarkers, 2006
    Co-Authors: Michael E Davis, Michal P Lisowyj, Sidney S Mirvish
    Abstract:

    Fifth AACR International Conference on Frontiers in Cancer Prevention Research, Nov 12-15, 2006 A65 Introduction: We report here further studies on factors affecting fecal apparent total N-Nitroso Compounds (ANC) in mice. This project concerns the hypothesis that N-Nitroso Compounds (NOC) in the colon contents are a significant cause of human colon cancer. Our previous research demonstrated that feeding beef and hot dogs increased fecal NOC excretion in mice and that a purified nitrosated ANC precursor in hot dogs was directly mutagenic in the Ames test and contained a Compound provisionally identified as N-glucosyl glycine. In other experiments on factors affecting fecal ANC output in mice, we reported that feeding NaNO2 (1 or 2 g/L drinking water) increased fecal ANC output and 1% hemin fed with NaNO2 increased fecal ANC two-fold compared to feeding nitrite alone. We now report additional experiments on factors affecting fecal ANC output in mice. Methods: Male 6-week-old Swiss mice were generally fed AIN-93G semipurified diet and tap water, and were treated in various ways for 7 days. Control groups were included in each experiment. Each group contained 4-27 (mean, 9) mice. During the last 24 h feces was collected from individual mice. Total 24-h feces for each mouse was dried at 0oC to constant weight, and extracted with water. Each extract was analyzed in duplicate for total NOC as before. Results: Treatments and results in nmol ANC/g, mean ± SE, were: (a) For 1000, 250 and 64 mg NaNO2/L drinking water; 21 ± 2, 9 ± 2, and 7 ± 1 (7.0, 2.3 and 3.5 x untreated controls); (b) for 2 g NaNO2/L water plus 250, 125 and 64 mg hemin/kg diet, 233 ± 49, 135 ± 19 and 138 ± 27 (4.6, 2.2 and 2.3 x control with 2 g NaNO2/L alone); (c) for 1 g NaNO2/L water plus 23 g Na ascorbate/kg diet, 17 ± 4 (0.59 x control with 1 g NaNO2/L alone); (d) for 1 g NaNO2/L water plus 400 mg omeprazole/kg diet, 3 ± 1 (0.20 x control with 1 g NaNO2/L alone); (e) for 1 g NaNO2/L water plus 18% hot dogs in diet, 59 ± 4 (2.6 x control with hot dog alone). Discussion: We confirmed the finding that nitrite alone increased fecal NOC output. As little as 64 mg NaNO2/L significantly increased fecal ANC level 3.5 times. Hemin increased fecal NOC output when fed with nitrite. As little as 64 mg hemin/kg diet significantly increased fecal NOC levels. The finding for hemin supports findings by others that heme or hemin increases fecal ANC levels in humans and promotes colon carcinogenesis in rats. The findings that NOC output was lowered when ascorbate or omeprazole was fed with nitrite support our view that nitrite produces ANC by an acid-catalyzed reaction in the stomach and that the resulting ANC pass down the gut to the feces. Support: National Cancer Institute RO3 grant CA-11753 and core grant P30-CA-36727.

  • partial purification from hot dogs of n Nitroso Compound precursors and their mutagenicity after nitrosation
    Journal of Agricultural and Food Chemistry, 2006
    Co-Authors: Lin Zhou, James Haorah, Fulvio Perini, Steven G Carmella, Takayuki Shibamoto, Sidney S Mirvish
    Abstract:

    Hot dogs contain apparent N-Nitroso Compounds (ANC) and ANC precursors (ANCP). ANCP purification was followed by nitrosation, sulfamic acid treatment, and analysis for ANC. Aqueous hot dog extracts were adsorbed on silica gel, which was eluted with MeCN and MeOH. The MeOH eluate was adsorbed on cation exchange resin (H+ form) and eluted with NH4OH. Eluted ANCP traveled at moderate speeds in high-performance liquid chromatography (HPLC) on amino and Pb2+ columns. Gas chromatography−mass spectrometry (GC-MS) of trimethylsilyl (TMS) derivatives of crude water extract indicated the presence of glycerol, phosphate, lactic acid, and two monosaccharides. GC-MS of TMS derivatives of Pb2+ column HPLC eluates indicated that ANCP included 1-deoxy-N-1-glucosyl glycine. The nitrosated NH4OH eluate showed 4× background mutagenic activity for Salmonella typhimurium TA-100. Un-nitrosated fractions showed 2× background activity. Although tryptophan nitrosation gave 88% ANC yield, tryptophan is probably not a major ANCP in...

  • levels of water extractable n Nitroso Compound and n Nitroso Compound precursor in 6 brands of snuff
    2004
    Co-Authors: Michael Belling, Lin Zhou, Sidney S Mirvish
    Abstract:

    Snuff conains substances known as water-extractable N-Nitroso Compounds (NOC) (Haorah et al., J. Agric. Food Chem. 49:6068, 2001). These NOC are derived from NOC precursors (NOCP). NOCP are amines or amides that are converted to NOC when they react with nitrite (are nitrosated). NOC obtained from nitrosation of NOCP in snuff were mutagenic in bacteria (unpublished). NOCP levels in snuff are much higher then NOC levels. We determined water-extractable NOC and NOCP levels in 4 commercial snuff brands (Grizzly, Timber Wolf, Skoal, and Copenhagen) and two non-commercial brands from Star Scientific (Ariva, and Stonewall) using a Thermal En ergy Analyzer (TEA). In some tests, solvent-extractable tobacco-specific nitrosamines, e.g. NNN and NNK, and their amine precursors, e.g. nornicotine, were removed by dichloromethane extraction from aqueous solutions brought to pH 12, and water extracts were re-analyzed. Grizzly, Timber Wolf, Skoal, and Coppenhagen snuff had total NOC levels of 320, 720, 230, and 110 nmol/g (measured after adding sulfamic acid). After extraction from alkali, three brands had 20-32% losses in NOC, but Coppenhagen had a 14% increase in NOC level. NOCP levels were determined by treating water extracts with 110 mm nitrite and then with sulfamic acid. The four commercial brands had NOCP values of 13-16 µmol/g snuff. After extraction from alkali, the 4 brands showed a 2751% loss of NOCP. Ariva and Stonewall snuff showed 0.36 and 0.46 nmol/g NOC and 14-19 µmol/g NOCP. Results suggest that water-extractable NOC and, perhaps, NOCP may help cause snuff-induced oral cancer, in addition to nitrosamines NNN and NNK, which should be extractable by dichloromethane. The Star Scientific brands, known to have very low levels of NNN and NNK, showed very low water-extractable NOC levels indicating their safety if these NOC are hazardous, but their high levels of NOCP could be a concern if they were nitrosated in the mouth.

  • experimental evidence for inhibition of n Nitroso Compound formation as a factor in the negative correlation between vitamin c consumption and the incidence of certain cancers
    Cancer Research, 1994
    Co-Authors: Sidney S Mirvish
    Abstract:

    Abstract Ascorbic acid (ASC) consumption is negatively correlated with the incidence of certain cancers. This is a review and update of the theory, which has recently been neglected, that this negative correlation is due to ASC inhibition of in vivo nitrosation. The review covers the older literature on ASC inhibition of carcinogenesis by nitrite administered with amines or amides and more recent studies on ASC inhibition of nitrosation by bacteria, nitrogen oxides, and activated macrophages; the role of oxygen in ASC inhibition of gastric nitrosation; ASC inhibition of N-Nitrosoproline formation in subjects from areas with high incidences of certain cancers; dose and temporal relationships between ASC and in vivo nitrosation in humans; the role of substances other than ASC in the inhibition of nitrosation by vegetables and fruits; and the active secretion of ASC into the human stomach.

Bruce S. King - One of the best experts on this subject based on the ideXlab platform.

  • direct and nitroxyl hno mediated reactions of acyloxy Nitroso Compounds with the thiol containing proteins glyceraldehyde 3 phosphate dehydrogenase and alkyl hydroperoxide reductase subunit c
    Journal of Medicinal Chemistry, 2013
    Co-Authors: Susan Mitroka, Mai E. Shoman, Jenna F. Dumond, Landon Bellavia, Omar M. Aly, Mohamed Abdelaziz, Daniel B Kimshapiro, Bruce S. King
    Abstract:

    Nitroxyl (HNO) reacts with thiols, and this reactivity requires the use of donors with 1-Nitrosocyclohexyl acetate, pivalate, and trifluoroacetate, forming a new group. These acyloxy Nitroso Compounds inhibit glyceraldehyde 3-phosphate dehydrogenase (GAPDH) by forming a reduction reversible active site disulfide and a reduction irreversible sulfinic acid or sulfinamide modification at Cys244. Addition of these acyloxy Nitroso Compounds to AhpC C165S yields a sulfinic acid and sulfinamide modification. A potential mechanism for these transformations includes nucleophilic addition of the protein thiol to a Nitroso Compound to yield an N-hydroxysulfenamide, which reacts with thiol to give disulfide or rearranges to sulfinamides. Known HNO donors produce the unsubstituted protein sulfinamide as the major product, while the acetate and pivalate give substituted sulfinamides that hydrolyze to sulfinic acids. These results suggest that Nitroso Compounds form a general class of thiol-modifying Compounds, allowing...

  • Direct and Nitroxyl (HNO)-Mediated Reactions of Acyloxy Nitroso Compounds with the Thiol-Containing Proteins Glyceraldehyde 3‑Phosphate Dehydrogenase and Alkyl Hydroperoxide Reductase Subunit C
    2013
    Co-Authors: Susan Mitroka, Mai E. Shoman, Jenna F. Dumond, Landon Bellavia, Omar M. Aly, Mohamed Abdel-aziz, Daniel B. Kim-shapiro, Bruce S. King
    Abstract:

    Nitroxyl (HNO) reacts with thiols, and this reactivity requires the use of donors with 1-Nitrosocyclohexyl acetate, pivalate, and trifluoroacetate, forming a new group. These acyloxy Nitroso Compounds inhibit glyceraldehyde 3-phosphate dehydrogenase (GAPDH) by forming a reduction reversible active site disulfide and a reduction irreversible sulfinic acid or sulfinamide modification at Cys244. Addition of these acyloxy Nitroso Compounds to AhpC C165S yields a sulfinic acid and sulfinamide modification. A potential mechanism for these transformations includes nucleophilic addition of the protein thiol to a Nitroso Compound to yield an N-hydroxysulfenamide, which reacts with thiol to give disulfide or rearranges to sulfinamides. Known HNO donors produce the unsubstituted protein sulfinamide as the major product, while the acetate and pivalate give substituted sulfinamides that hydrolyze to sulfinic acids. These results suggest that Nitroso Compounds form a general class of thiol-modifying Compounds, allowing their further exploration

Léon Ghosez - One of the best experts on this subject based on the ideXlab platform.

Susan Mitroka - One of the best experts on this subject based on the ideXlab platform.

  • direct and nitroxyl hno mediated reactions of acyloxy Nitroso Compounds with the thiol containing proteins glyceraldehyde 3 phosphate dehydrogenase and alkyl hydroperoxide reductase subunit c
    Journal of Medicinal Chemistry, 2013
    Co-Authors: Susan Mitroka, Mai E. Shoman, Jenna F. Dumond, Landon Bellavia, Omar M. Aly, Mohamed Abdelaziz, Daniel B Kimshapiro, Bruce S. King
    Abstract:

    Nitroxyl (HNO) reacts with thiols, and this reactivity requires the use of donors with 1-Nitrosocyclohexyl acetate, pivalate, and trifluoroacetate, forming a new group. These acyloxy Nitroso Compounds inhibit glyceraldehyde 3-phosphate dehydrogenase (GAPDH) by forming a reduction reversible active site disulfide and a reduction irreversible sulfinic acid or sulfinamide modification at Cys244. Addition of these acyloxy Nitroso Compounds to AhpC C165S yields a sulfinic acid and sulfinamide modification. A potential mechanism for these transformations includes nucleophilic addition of the protein thiol to a Nitroso Compound to yield an N-hydroxysulfenamide, which reacts with thiol to give disulfide or rearranges to sulfinamides. Known HNO donors produce the unsubstituted protein sulfinamide as the major product, while the acetate and pivalate give substituted sulfinamides that hydrolyze to sulfinic acids. These results suggest that Nitroso Compounds form a general class of thiol-modifying Compounds, allowing...

  • Direct and Nitroxyl (HNO)-Mediated Reactions of Acyloxy Nitroso Compounds with the Thiol-Containing Proteins Glyceraldehyde 3‑Phosphate Dehydrogenase and Alkyl Hydroperoxide Reductase Subunit C
    2013
    Co-Authors: Susan Mitroka, Mai E. Shoman, Jenna F. Dumond, Landon Bellavia, Omar M. Aly, Mohamed Abdel-aziz, Daniel B. Kim-shapiro, Bruce S. King
    Abstract:

    Nitroxyl (HNO) reacts with thiols, and this reactivity requires the use of donors with 1-Nitrosocyclohexyl acetate, pivalate, and trifluoroacetate, forming a new group. These acyloxy Nitroso Compounds inhibit glyceraldehyde 3-phosphate dehydrogenase (GAPDH) by forming a reduction reversible active site disulfide and a reduction irreversible sulfinic acid or sulfinamide modification at Cys244. Addition of these acyloxy Nitroso Compounds to AhpC C165S yields a sulfinic acid and sulfinamide modification. A potential mechanism for these transformations includes nucleophilic addition of the protein thiol to a Nitroso Compound to yield an N-hydroxysulfenamide, which reacts with thiol to give disulfide or rearranges to sulfinamides. Known HNO donors produce the unsubstituted protein sulfinamide as the major product, while the acetate and pivalate give substituted sulfinamides that hydrolyze to sulfinic acids. These results suggest that Nitroso Compounds form a general class of thiol-modifying Compounds, allowing their further exploration