Carcinogenic N-nitroso Compounds Research Articles

NDMA enhances claudin-1 and -6 expression viaCYP2E1/ROS in AGS cells

Carcinogenic N-nitroso compounds, especially N-nitroso dimethylamine, increase the risk of gastric cancer development. Cytochrome P450-2E1 metabolizes this compound, thus generating an oxidant microenvironment. We aimed to evaluate in gastric adenocarcinoma cells if its effect on CYP2E1 and ROS affects signaling pathways associated with gastric cancer oncogenesis. The impact of N- nitroso dimethylamine upon CYP2E1 and ROS activation/secretion was evaluated by the DCFDA assay protocol, TER measurements, Stat3, pSTAT3, ERK1/2, and pERK1/2 expression, claudins-1 and -6 expression, and finally mRNA values of IL-1β IL-6, IL-8 and TNFα. Our results showed that exposure to N- N-nitroso dimethylamine disrupts the regulation of Stat3 and Erk1/2, alters the expression of claudin-1 and claudin-6 tight junction proteins, and increases the secretion of pro-inflammatory cytokines. These alterations induce a continuous local inflammatory process, an event identified as a gastric cancer promoter. In summary, N-nitroso dimethylamine can disrupt cell mechanisms associated with gastric cancer oncogenesis.

Source-specific nitrate intake and all-cause mortality in the Danish Diet, Cancer, and Health Study

IntroductionNitrate and nitrite are naturally occurring in both plant- and animal-sourced foods, are used as additives in the processing of meat, and are found in water. There is growing evidence that they exhibit a spectrum of health effects, depending on the dietary source. The aim of the study was to examine source-dependent associations between dietary intakes of nitrate/nitrite and both all-cause and cause-specific mortality.MethodsIn 52,247 participants of the Danish Diet, Cancer and Health Study, associations between source-dependent nitrate and nitrite intakes––calculated using comprehensive food composition and national drinking water quality monitoring databases––and all-cause, cardiovascular disease (CVD)-related, and cancer-related mortality over 27 years were examined using restricted cubic splines within Cox proportional hazards models adjusting for demographic, lifestyle, and dietary confounders. Analyses were stratified by factors hypothesised to influence the formation of carcinogenic N-nitroso compounds (namely, smoking and dietary intakes of vitamin C, vitamin E, folate, and polyphenols).ResultsPlant-sourced nitrate intake was inversely associated with all-cause mortality [HRQ5vsQ1: 0.83 (0.80, 0.87)] while higher risks of all-cause mortality were seen for higher intakes of naturally occurring animal-sourced nitrate [1.09 (1.04, 1.14)], additive permitted meat-sourced nitrate [1.19 (1.14, 1.25)], and tap water-sourced nitrate [1.19 (1.14, 1.25)]. Similar source-dependent associations were seen for nitrite and for CVD-related and cancer-related mortality except that naturally occurring animal-sourced nitrate and tap water-sourced nitrate were not associated with cancer-related mortality and additive permitted meat-sourced nitrate was not associated with CVD-related mortality. No clear patterns emerged in stratified analyses.ConclusionNitrate/nitrite from plant sources are inversely associated while those from naturally occurring animal-sources, additive-permitted meat sources, and tap water-sources are positively associated with mortality.

Ingested nitrate and nitrite and end-stage renal disease in licensed pesticide applicators and spouses in the Agricultural Health Study

BackgroundNitrate and nitrite ingestion has been linked to kidney cancer, possibly via the endogenous formation of carcinogenic N-nitroso compounds. These exposures might also contribute to end-stage renal disease (ESRD).ObjectivesWe investigated associations of drinking water nitrate and dietary nitrate and nitrite intakes (total and by food type) with incident ESRD in the Agricultural Health Study. We also explored modifying effects of vitamin C and heme iron intake, which may affect endogenous nitrosation.MethodsWe performed complete case analyses among private pesticide applicators and their spouses. We obtained water nitrate estimates for participants whose primary drinking water source at enrollment (1993−1997) was public water supplies (PWS) or private wells (N = 59,632). Average nitrate concentrations were computed from historical data for PWS users and predicted from random forest models for private well users. Analysis of dietary nitrate and nitrite was restricted to the 30,177 participants who completed the NCI Dietary History Questionnaire during follow-up (1999−2003). Incident ESRD through 2018 was ascertained through linkage with the U.S. Renal Data System. We estimated adjusted hazard ratios (HRs) and 95%CI for associations of tertiles (T) of exposure with ESRD overall and explored effects in strata of vitamin C and heme iron intake.ResultsWe identified 469 incident ESRD cases (206 for dietary analysis). Water nitrate and total dietary nitrate/nitrite were not associated with ESRD, but increased ESRD was associated with nitrate and nitrite from processed meats. We found apparent associations between nitrite and ESRD only among participants with vitamin C <median (T3 vs. T1 HR: 2.26, 95%CI: 1.05, 4.86) and with heme iron ≥median (T3 vs. T1 HR: 1.73, 95%CI: 0.89, 3.39).SignificanceESRD incidence was associated with dietary nitrate/nitrite from processed meat among all study participants and with total dietary nitrite among participants with lower vitamin C or higher heme iron intake.Impact statementThere are few well-established environmental risk factors for end-stage renal disease (ESRD), a worldwide public health challenge. Ingestion of nitrate and nitrite, which may lead to endogenous formation of carcinogenic N-nitroso compounds, has been linked to some cancers and chronic diseases. We investigated these exposures in relation to ESRD in an agricultural cohort. ESRD incidence was associated with dietary nitrate/nitrite from processed meat and with total dietary nitrite among subgroups with lower vitamin C or higher heme iron intake. This study provides preliminary evidence that points to dietary nitrite and possibly dietary nitrate intake as a potential contributor to ESRD.

Influence of Biochar and Animal Manures Application on Ammonia and Nitrate Concentrations in the Root and Shoot of Three Varieties of Turnips

Many investigators have focused on the impact of fertilizers on crop yield and ignored fertilizers impact on the plants composition. The impact of seven types of soil treatments (sewage sludge, horse manure, chicken manure, vermicompost, elemental organic fertilizer, inorganic fertilizer, and native soil) and similar seven treatments amended with biochar on the concentrations of NH3 and NO3 in the roots and shoots of three commercial varieties of turnips, Brassica rapa was investigated. The three varieties (Purple Top White Globe PTWG, Scarlet Queen Red SQR, and Tokyo Cross TC) varied in concentrations of NH3 and NO3 levels. High levels of NO3 in edible plants is associated with harmful effects on human health, due to the risk of creation of carcinogenic N-nitroso compounds. NO3 in SQR roots and shoots (edible greens) was greater than varieties PTWG and TC. The concentration of NH3 averaged 20.2, 12.8, and 8.9 µg g−1 fresh turnip roots, whereas NO3 values averaged 107.6, 64.1, and 62.9 µg g−1 fresh turnip roots in varieties SQR, PTWG, and TC, respectively. Regardless of soil amendment type, the concentration of NH3 in the shoots (44.0 µg g−1) was greater than the roots (15 µg g−1). On the contrary, NO3 was higher in the roots (89.4 µg g−1) compared to the shoots (67.6 µg g−1 fresh tissue). Overall, biochar added to vermicompost amended soil increased NH3 by 73% compared to vermicompost not amended with biochar. Regarding acceptable daily intake (ADI) for NO3, none of the three varieties analyzed constitute any NO3 adverse effects on normal human intake. Similarly, consuming turnips grown in any of the animal manures tested do not represent any hazardous issues.

Arginine metabolism and the role of arginine deiminase-producing microorganisms in kimchi fermentation

In this study, we evaluated the correlation between the arginine deiminase (ADI) pathway and nitrogen cycle during cabbage kimchi fermentation. Nitrite used as a food additive can be converted to carcinogenic N-nitroso compounds via reactions with secondary amines under specific conditions; thus, high nitrate- and nitrite-containing foods present a potential risk to human health. We monitored the bacterial community, levels of ADI metabolites, and nitrogen compounds present in kimchi that contained bacteria that showed low ADI activity during fermentation. The dominant growth of microorganisms with weak ADI activity reduced arginine degradation and ornithine production. Furthermore, nitrite production in kimchi samples was affected by ADI activity. The ornithine and nitrite contents in the control kimchi were 1.7- and 2.6-fold higher at week 2 than at week 1. These results suggest that ADI-associated metabolism is correlated with the nitrogen cycle in kimchi and that the addition of bacteria with weak ADI activity may reduce nitrite production in kimchi.

Analysis of human serum and urine for tentative identification of potentially carcinogenic pesticide-associated N-nitroso compounds using high-resolution mass spectrometry

Human serum and urine samples were analyzed for a suite of nitrosatable pesticides and potentially carcinogenic pesticide-associated N–nitroso (PANN) compounds. Formation of PANN compounds may occur in vivo after consumption of food or water containing trace amounts of nitrosatable pesticide residues and nitrate. Using a modified version of the Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) method, nine nitrosatable pesticides and byproducts were extracted from serum and urine from 64 individuals from two different sample populations in Atlantic Canada: (i) Prince Edward Island, a region where nitrate and trace amounts of nitrosatable pesticides have been detected in groundwater; and (ii) Halifax, Nova Scotia, a non-agricultural urban area. Samples were then analyzed using ultra-high pressure liquid chromatography (UHPLC) coupled with high-resolution accurate mass (HRAM) single-stage orbitrap mass spectrometry (MS), which allows for semi-targeted analysis and tentative identification of a virtually limitless number of exposure biomarkers. Two nitrosatable target analytes, ethylenethiourea (ETU) and 3,5,6-trichloro-2-pyridinol (TCPy) were found in serum, while atrazine (ATR) and ETU were detected in urine. Five and six PANN compounds were tentatively identified in serum and urine, respectively. The two PANN compounds that were most frequently tentatively identified in serum were N-nitroso dimethoate (N-DIM) and N-nitroso omethoate (N-OME) with detection frequencies of 78% and 95%, respectively. This is the first biomonitoring study of its kind to investigate PANN compounds in human serum and urine.

Effects of processed meat and drinking water nitrate on oral and fecal microbial populations in a controlled feeding study

BackgroundOne mechanism that can explain the link between processed meat consumption and colorectal cancer (CRC) is the production of carcinogenic N-nitroso compounds (NOCs) in the gastrointestinal tract. Oral and gut microbes metabolize ingested proteins (a source of secondary and tertiary amines and amides) and can reduce nitrate to nitrite, generating potentially carcinogenic NOCs. ObjectiveWe evaluated whether nitrate/nitrite in processed meat or water influences the fecal or salivary microbiota. DesignIn this dietary intervention study, 63 volunteers consumed diets high in conventional processed meats for two weeks, switched to diets high in poultry for two weeks, and then consumed phytochemical-enriched conventional processed or low-nitrite processed meat diets for two weeks. During the intervention, they drank water with low nitrate concentrations and consumed a healthy diet with low antioxidants. Then the volunteers drank nitrate-enriched water for 1 week, in combination with one of the four different diets. We measured creatinine-adjusted urinary nitrate levels and characterized the oral and fecal microbiota using 16S rRNA amplicon sequencing. ResultsUsing linear mixed models, we found that, compared to baseline, urinary nitrate levels were reduced during the phytochemical-enriched low-nitrite meat diet (p-value = 0.009) and modestly during the poultry diet (p-value = 0.048). In contrast, urinary nitrate increased after 1-week of drinking nitrate-enriched water (p-value<10−5). Nitrate-enriched water, but not processed meats with or without phytochemicals, altered the saliva microbial population (p-value ≤0.001), and significantly increased abundance of 8 bacterial taxa, especially genus Neisseria and other nitrate-reducing taxa. Meats, phytochemicals and nitrate-enriched water had no significant effects on saliva alpha diversity or any diversity parameter measured for the fecal microbiota. ConclusionThese findings support the hypothesis that drinking high nitrate water increases oral nitrate-reducing bacteria, which likely results in increased NOC. However, meat nitrate/nitrite at the levels tested had no effect on either the gut or oral bacteria. ClinicalTrials.gov IdentifierNCT04138654.

Salivary Microbiota for Gastric Cancer Prediction: An Exploratory Study.

To characterize the salivary microbiota in patients at different progressive histological stages of gastric carcinogenesis and identify microbial markers for detecting gastric cancer, two hundred and ninety-three patients were grouped into superficial gastritis (SG; n = 101), atrophic gastritis (AG; n = 93), and gastric cancer (GC; n = 99) according to their histology. 16S rRNA gene sequencing was used to access the salivary microbiota profile. A random forest model was constructed to classify gastric histological types based on the salivary microbiota compositions. A distinct salivary microbiota was observed in patients with GC when comparing with SG and AG, which was featured by an enrichment of putative proinflammatory taxa including Corynebacterium and Streptococcus. Among the significantly decreased oral bacteria in GC patients including Haemophilus, Neisseria, Parvimonas, Peptostreptococcus, Porphyromonas, and Prevotella, Haemophilus, and Neisseria are known to reduce nitrite, which may consequently result in an accumulation of carcinogenic N-nitroso compounds. We found that GC can be distinguished accurately from patients with AG and SG (AUC = 0.91) by the random forest model based on the salivary microbiota profiles, and taxa belonging to unclassified Streptophyta and Streptococcus have potential as diagnostic biomarkers for GC. Remarkable changes in the salivary microbiota functions were also detected across three histological types, and the upregulation in the isoleucine and valine is in line with a higher level of these amino acids in the gastric tumor tissues that reported by other independent studies. Conclusively, bacteria in the oral cavity may contribute gastric cancer and become new diagnostic biomarkers for GC, but further evaluation against independent clinical cohorts is required. The potential mechanisms of salivary microbiota in participating the pathogenesis of GC may include an accumulation of proinflammatory bacteria and a decline in those reducing carcinogenic N-nitroso compounds.

Study on sulfur vulcanized natural rubber formulated with nitrosamine safe diisopropyl xanthogen polysulfide/tertiary butyl benzothiazole sulphenamide binary accelerator system

An outstanding interest on elimination of nitrosamine generation in traditional sulfur vulcanization systems has led to introduce nitrosamine safe accelerator/s to produce safe natural rubber (NR) vulcanizates. It is an effective way to prevent formation of carcinogenic N-nitroso compounds during manufacture of rubber products. In the present study, behavior of nitrosamine safe binary accelerator system consisting of diisopropyl xanthogen polysulfide (DIXP) with commonly used non-regulated accelerator N-tert-butyl-2-benzothiazole sulfenamide (TBBS) was investigated in efficient sulfur vulcanization of NR. Cure characteristics, physico-mechanical properties and crosslink density of vulcanizates prepared with different combinations of the accelerator system were evaluated and compared with those of individual accelerators. The study reveals that moduli and strength properties of the vulcanizate prepared with DIXP accelerator are inferior to those of the vulcanizate prepared with TBBS accelerator. Nevertheless, optimum cure time of the DIXP compounds is lower in comparison to TBBS compounds. Moreover, progressive replacement of DIXP with TBBS in the accelerator system showed a synergistic effect in regard to cure characteristics and physico-mechanical properties.

Reduction in biogenic amines in douchi fermented by probiotic bacteria.

Ecology studies showed that esophageal and gastric cancers are directly correlated with the consumption of processed foods. The carcinogenicity of traditional Chinese fermented foods such as douchi (fermented black beans or fermented black soybeans) is due to the presence of carcinogenic N-nitroso compounds, which are derived from biogenic amines. Among the various biogenic amines that can act as precursors of N-nitroso compounds, histamine and tyramine are considered to be the most toxic and are of public health concern when present in food. We have examined some douchi products on the market, and significant amounts of histamine and tyramine were found. The use of fermentation starters generated by subculturing fermented products with unknown microbiota would induce the risk of biogenic amines. As the microbiota used in fermentation is a crucial factor in determining the biogenic amines of fermented food, it is hypothesized that the possible harmful effects of douchi can be minimized through the use of fermentation starters composed of probiotic bacteria. This is the first study to investigate the potential of using probiotic bacteria in manufacturing douchi. Lactobacillus rhamnosus GG (LGG), Lactobacillus casei Shirota (LcS) and Escherichia coli Nissle 1917 (EcN) were used to ferment black beans in this study, and no tyramine was detected in black bean samples incubated with these three strains anaerobically at 37°C or 20°C. The starter culture strains, temperature and presence of oxygen during the incubation period were found to be critical to the generation of biogenic amines. The findings of this study can provide evidence-based insights and warrant further investigations on the potential of reducing the harmful compounds in food fermented with probiotic bacteria as well as the sensory evaluation of douchi fermented with probiotic bacteria.

Inulin-fortification of a processed meat product attenuates formation of nitroso compounds in the gut of healthy rats

Intake of red and processed meat has been suspected to increase colorectal cancer risk potentially via endogenous formation of carcinogenic N-nitroso compounds or increased lipid and protein oxidation. Here we investigated the effect of inulin fortification of a pork sausage on these parameters. For four weeks, healthy Sprague-Dawley rats (n = 30) were fed one of three diets: inulin-fortified pork sausage, control pork sausage or a standard chow diet. Fecal content of apparent total N-nitroso compounds (ATNC), nitrosothiols and nitrosyl iron compounds (FeNO) were analyzed in addition to liver metabolism and oxidation products formed in liver, plasma and diets. Intriguingly, inulin fortification reduced fecal ATNC (p = 0.03) and FeNO (p = 0.04) concentrations. The study revealed that inulin fortification of processed meat could be a strategy to reduce nitroso compounds formed endogenously after consumption.

Comparison of sample preparation approaches and validation of an extraction method for nitrosatable pesticides and metabolites in human serum and urine analyzed by liquid chromatography – Orbital ion trap mass spectrometry

In the acidic environment of the stomach, nitrosatable pesticide residues may react with nitrite to form potentially carcinogenic pesticide-associated N-nitroso compounds (PANOCs). The objective of this study was to develop a method for the analysis of 10 nitrosatable pesticides and breakdown products in human serum and urine. Three sample preparation methods were evaluated for extraction of target analytes from the biomatrices. Deproteinization by methanol for 300-μL aliquots of serum with a final extract volume of 225 μL resulted in excessive ion enhancement of some analytes and suppression of others. Three types of solid-phase extraction cartridges were tested for optimal analyte retention from 200-μL aliquots of serum with a final extract volume of 400 μL; this approach resulted in significant analyte loss for some compounds. The Quick, Easy, Cheap, Effective, Rugged, and Safe approach resulted in a suitable method for extraction of the analytes from each biomatrix. Biofluid samples (500 μL) were spiked to 100 μg L−1 with analytical standards and extracted using 500 μL of acetonitrile (ACN) with 4% acetic acid (AcOH) for serum and 0.1% AcOH in ACN for urine. For extraction, 200 mg magnesium sulfate (MgSO4) and 50 mg sodium acetate were added for serum and 200 mg MgSO4 and 50 mg sodium chloride were added for urine. Final extract volumes for both biomatrices using the QuEChERS method was 400 μL after dilution. Samples were analyzed via ultra-high pressure liquid chromatography/high-resolution accurate mass orbital ion trap mass spectrometry. Mean recoveries for target analytes in serum and urine ranged between 74 and 120% (%RSD < 12) and 96 to 116% (%RSD ≤ 10), respectively. These methods may be used in large-scale biomonitoring studies to analyze PANNs and their parent compounds in human serum and urine.

Mechanistic Evidence for Red Meat and Processed Meat Intake and Cancer Risk: A Follow-up on the International Agency for Research on Cancer Evaluation of 2015.

The Working Group of the International Agency for Research on Cancer classified the consumption of processed meat as carcinogenic to humans (Group 1), and classified red meat as probably carcinogenic to humans (Group 2A); consumption of both meat types is associated with an increased risk of colorectal cancer. These classifications are based on a compilation of epidemiology data and mechanistic evidence from animal and human studies. The curing of meats with nitrite can produce carcinogenic N-nitroso compounds (NOCs), and the smoking of meat produces polycyclic aromatic hydrocarbons (PAHs). The high-temperature cooking of meat also produces carcinogenic heterocyclic aromatic amines (HAAs). The ingestion of heme from meat can catalyze the formation of NOCs and lipid peroxidation products (LPOs) in the digestive tract. Many of these chemicals form DNA adducts, some of which can induce mutations and initiate carcinogenesis. Another recent hypothesis is that N-glycolylneuraminic acid, a non-human sialic acid sugar present in red meat, becomes incorporated in the cell membrane, triggering the immune response with associated inflammation and reactive oxygen species, which can contribute to DNA damage, tumor promotion, and cancer. The mechanisms by which these chemicals in meat induce DNA damage, and the impact of dietary and host factors that influence the biological potency of these chemicals are highlighted in this updated report.

Haem iron intake and risk of lung cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

BackgroundEpidemiological studies suggest that haem iron, which is found predominantly in red meat and increases endogenous formation of carcinogenic N-nitroso compounds, may be positively associated with lung cancer. The objective was to examine the relationship between haem iron intake and lung cancer risk, using detailed smoking history data and serum cotinine to control for potential confounding.MethodsIn the European Prospective Investigation into Cancer and Nutrition (EPIC), 416 746 individuals from ten countries completed demographic and dietary questionnaires at recruitment. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for incident lung cancer (n=3 731) risk relative to haem iron, non-haem iron, and total dietary iron intake. A corresponding analysis was conducted among a nested subset of 800 lung cancer cases and 1,489 matched controls for whom serum cotinine was available.ResultsHaem iron was associated with lung cancer risk, including after adjustment for details of smoking history (time since quitting, number of cigarettes per day): as a continuous variable (HR per 0.3 mg/1000 kcal 1.03, 95% CI 1.00 – 1.07), and in the highest versus lowest quintile (HR 1.16, 95%CI 1.02 – 1.32; trend across quintiles: P = 0.035). In contrast, non-haem iron intake was related inversely with lung cancer risk; however, this association attenuated after adjustment for smoking history. Additional adjustment for serum cotinine did not considerably alter the associations detected in the nested case-control subset.ConclusionsGreater haem iron intake may be modestly associated with lung cancer risk.

Evaluation of the antimicrobial capacity of Hass avocado seed extract (Persea americana) for potential application in the meat industry

NaNO2 is used in meat products to inhibit pathogenic microorganisms; its use is limited, and it forms carcinogenic N-nitroso compounds. There is currently a great demand for natural products. The Hass avocado seed extract produces an antimicrobial reaction against bacteria such as Staphylococcus aureus. After the seed of the Hass avocado (AS) had been dehydrated at 50°C for 10 hours, we undertook a quality and analysis of the moisture and microbiological test. The extract was obtained in hot water and in solvents to perform an antimicrobial sensitivity test, which is an inhibition halo test using the strain Staphylococcus aureus as microorganisms. A minimum capacity inhibition test was also carried out. The concentration of the extract by solvents was 7 mg/mL, and it presented an inhibition halo of 1.8mm.The combination of AS and nitrites caused oxidation and darkening in the halos. The compounds that were extracted from the Hass avocado seeds with the methods used are not effective against S. aureus.

Role of vitamin C in gastric cancer

Gastric cancer is a multifactorial disease with complex interplay of environmental and genetic factors. Helicobacter pylori (H. pylori) infestation has been identified as the most important etiological agent in the pathogenesis of gastric cancer. Also, the role of dietary factors that is low consumption of fruits and vegetables have been found to be associated with gastric cancer. Among the dietary factors, antioxidants especially vitamin C has been found to confer the strongest protection against gastric cancer. Its anti-proliferative and pro-apoptotic action has been suggested in vitro. Because of its antioxidant activity, it protects cells against oxidative DNA damage caused by toxic effects of reactive oxygen species. It also inhibits production of carcinogenic N-nitroso compound in the stomach. The person with H. pylori infection has low levels of vitamin C in their gastric juice and levels of vitamin C normalizes on eradication of H. pylori. Vitamin C levels are high in gastric mucosa and gastric juice, sometimes more than that of in plasma. But gastric pathological conditions cause lowered secretion of vitamin C into gastric juice. Effect of H. pylori on vitamin C in gastric juice is reversible and on eradication of H. pylori, it returns to normal level. Hence, eradication of H. pylori and chemoprevention with antioxidant supplementation will be an effective preventive strategy to reduce the incidence of gastric cancer and related mortality. Vitamin C and gastric cancer is an area of potential interest for researchers as a preventive measure. Keywords: Vitamin C, H. pylori, gastric cancer.

Role of vitamin C in gastric cancer

Gastric cancer is a multifactorial disease with complex interplay of environmental and genetic factors. Helicobacter pylori (H. pylori) infestation has been identified as the most important etiological agent in the pathogenesis of gastric cancer. Also, the role of dietary factors that is low consumption of fruits and vegetables have been found to be associated with gastric cancer. Among the dietary factors, antioxidants especially vitamin C has been found to confer the strongest protection against gastric cancer. Its anti-proliferative and pro-apoptotic action has been suggested in vitro. Because of its antioxidant activity, it protects cells against oxidative DNA damage caused by toxic effects of reactive oxygen species. It also inhibits production of carcinogenic N-nitroso compound in the stomach. The person with H. pylori infection has low levels of vitamin C in their gastric juice and levels of vitamin C normalizes on eradication of H. pylori. Vitamin C levels are high in gastric mucosa and gastric juice, sometimes more than that of in plasma. But gastric pathological conditions cause lowered secretion of vitamin C into gastric juice. Effect of H. pylori on vitamin C in gastric juice is reversible and on eradication of H. pylori, it returns to normal level. Hence, eradication of H. pylori and chemoprevention with antioxidant supplementation will be an effective preventive strategy to reduce the incidence of gastric cancer and related mortality. Vitamin C and gastric cancer is an area of potential interest for researchers as a preventive measure. Keywords: Vitamin C, H. pylori, gastric cancer.

Nitrate in drinking water and colorectal cancer risk: A nationwide population-based cohort study.

Nitrate in drinking water may increase risk of colorectal cancer due to endogenous transformation into carcinogenic N-nitroso compounds. Epidemiological studies are few and often challenged by their limited ability of estimating long-term exposure on a detailed individual level. We exploited population-based health register data, linked in time and space with longitudinal drinking water quality data, on an individual level to study the association between long-term drinking water nitrate exposure and colorectal cancer (CRC) risk. Individual nitrate exposure was calculated for 2.7 million adults based on drinking water quality analyses at public waterworks and private wells between 1978 and 2011. For the main analyses, 1.7 million individuals with highest exposure assessment quality were included. Follow-up started at age 35. We identified 5,944 incident CRC cases during 23 million person-years at risk. We used Cox proportional hazards models to estimate hazard ratios (HRs) of nitrate exposure on the risk of CRC, colon and rectal cancer. Persons exposed to the highest level of drinking water nitrate had an HR of 1.16 (95% CI: 1.08-1.25) for CRC compared with persons exposed to the lowest level. We found statistically significant increased risks at drinking water levels above 3.87 mg/L, well below the current drinking water standard of 50 mg/L. Our results add to the existing evidence suggesting increased CRC risk at drinking water nitrate concentrations below the current drinking water standard. A discussion on the adequacy of the drinking water standard in regards to chronic effects is warranted.

Correlation of precancerous lesion incidence with duodenogastric reflux and N-nitroso compound duration at reflux and antireflux stomach surgery: An experimental study

Background/Aim. Duodenogastric reflux occurs after gastroenteroanastomosis, with or without resection of the stomach (Billroth I, Billroth II), after vagotomy and pyloroplasty, gastroduodenostomy as well as in conservatively treated patients. The aim of this study was to analyse the effect of carcinogenic N-nitroso compounds (MNNG) influence in conjunction with duodenogastric reflux, in the function of time for precancerous lesions development in gastric mucosa. A particular purpose of the study has been to suggest some effective surgical procedures, which could prevent the harmful effects of duodenogastric reflux on gastric mucosa, as a potential activator of carcinogenesis. Methods. The research included 90 experimental, male Wistar rats, divided into 3 groups. The two experimental groups were subjected to two surgical procedures: Billroth II gastric resection (group B2), and the Roux-en-Y reconstruction (group RY), respectively. The control group (group C) animals did not receive any surgical treatment. All groups were administered per os chemical cancerogen MNNG. All anastomoses were performed by extra mucosal suture with monofilament polypropilene 7?0, and 8?0. The animals were sacrificed consecutively, and subjected to total gastrectomy after 8, 16 and 24 weeks. Results. Pathohistological analysis was performed on defined regions of the rat stomach in three time period. The B2 group, at the end of our experiment, showed predominant incidence of severe lesions: hyperplasia (0%), gastritis (0%), metaplasia (6.7%), dysplasia (46.7%), early carcinoma (20%) and carcinoma (26.7%). At the end of our experiment, the RY and C groups showed the similarities of the obtained results related to time with predominant incidence of mild lesions: hyperplasia (13.3% vs 0%, respectively), gastritis (13.3% vs 13.3%, respectively), metaplasia (6.7% vs 13.3%, respectively), dysplasia (66.7% vs 66.7%, respectively), with an extremely low incidence of early carcinoma (0% vs 6.7%, respectively) and no incidence of carcinoma (0% vs 0%, respectively). Conclusion. Without the presence of duodenogastric reflux, MNNG causes a low degree of precancerous gastric lesions. However, direct contacts of MNNG with gastric mucosa, including the presence of duodenogastric reflux, induce precancerous lesions and carcinoma. The percentage of reversible changes decreases with time, while the percentage of irreversible lesions and carcinoma increases. A lack of distinction in the findings between the RY and C groups confirms a gastroprotective role of the Roux-en-Y procedure.

Perspectives in production of functional meat products

The meat industry has met new challenges since the World Health Organization classified processed meat in carcinogenic Group 1. In relation to this, the functional food concept in meat processing has gained importance, especially in reducing carcinogenic N-nitroso compounds and polycyclic aromatic hydrocarbons (PAHs) as an additional imperative, apart from the usual fat and salt reduction and product enrichment with functional ingredients. PAH reduction relies on control of the smoking process, but there is also a possibility they could be degraded by means of probiotic microorganisms or spices. The reduction of N-nitroso compounds could be provided by lowering the amount of added nitrite/nitrate, using substitutes for these chemicals, and/or by preventing conditions for the creation of N-nitroso compounds. Nevertheless, fat and salt reductions still remain topical, and rely mostly on the use of functional ingredients as their substitutes.