Search

Chemical carcinogen-induced oxidative stress has a key role in cell signaling linked to the development of cancer. Oxidative stress leads to oxidative damage to cellular membranes, proteins, chromosomes and genetic material. It is thought that compounds like hesperidin with high antioxidant and anticancer potential can reduce development of cancer induced by chemical carcinogens via neutralizing their oxidative damages. We investigated protective effect of hesperidin against N-Ethyl-N-Nitrosourea (ENU)-induced neurotoxicity, congenital abnormalities and possible brain cancer after exposure of mice during pregnancy as model of glioma. The mice were divided to four groups; control (normal saline), ENU (40 mg/kg daily for three consecutive days from the 17th to the 19th of pregnancy), hesperidin (pretreated with 25 mg/kg for 30 consecutive days, before mating) + ENU and hesperidin alone. Developmental toxicity parameters (the number of pregnant mice, stillbirths, abortion, live and dead offspring), behavioral tests (novel object recognition, open field and elevated plus maze) were performed. Moreover, the activity of butrylcholinesterase and acetylcholinesterase enzymes, oxidative markers and histopathological abnormalities were detected in brain tissue. Our data showed that conversely, the pretreatment of hesperidin reduces various degrees of developmental toxicity, neurobehavioral dysfunction, neurotoxicity, oxidative stress and histopathological abnormalities induced by ENU as a neurotoxic and carcinogenic agent in the next generation. In conclusion, pre-mating exposure with hesperidin may open new avenues for prevention of primary brain cancer in next generation and could be valuable for enhancing the antioxidant defense and minimizing the developmental and neurotoxicity of DNA alkylating agents. [ABSTRACT FROM AUTHOR]

Meat and meat products are important foods in the human diet, but there are concerns about their quality and safety. The discovery of carcinogenic and genotoxic N-nitroso compounds (NOCs) in processed meat products has had serious negative impacts on the meat industry. In order to clarify the relationship between the use of nitrite or nitrate and the safety of meat or meat products, we reviewed NOCs in meat and meat products, the origin and safety implications of NOCs, effects of nitrite and nitrate on meat quality, national regulations, recent publications concerning the using of nitrite and nitrate in meat or meat products, and reduction methods. By comparing and analyzing references, (1) we found antioxidant, flavor improvement and shelf-life extension effects were recently proposed functions of nitrite and nitrate on meat quality, (2) the multiple functions of nitrite and nitrate in meat and meat products couldn't be fully replaced by other food additives at present, (3) we observed that the residual nitrite in raw meat and fried meat products was not well monitored, (4) alternative additives seem to be the most successful methods of replacing nitrite in meat processing, currently. The health risks of consuming processed meat products should be further evaluated, and more effective methods or additives for replacing nitrite or nitrate are needed.

Humans are unavoidably exposed to numerous different mutagenic DNA alkylating agents (AAs), but their role in the initiation of cancers is uncertain, in part due to difficulties in assessing human exposure. To address this, we have developed a screening method that measures promutagenic O6-alkylguanines (O6-AlkGs) in DNA and applied it to human DNA samples. The method exploits the ability of the Schizosaccharomyces pombe alkyltransferase-like protein (Atl1) to recognise and bind to a wide range of O6-AlkGs in DNA. We established an Atl1-based slot-blot (ASB) assay and validated it using calf thymus DNA alkylated in vitro with a range of alkylating agents and both calf thymus and human placental DNA methylated in vitro with temozolomide (TMZ). ASB signals were directly proportional to the levels of O6-meG in these controls. Pre-treatment of DNA with the DNA repair protein O6-methylguanine–DNA methyltransferase (MGMT) reduced binding of Atl1, confirming its specificity. In addition, MCF 10A cells were treated with 500 μM TMZ and the extracted DNA, analysed using the ASB, was found to contain 1.34 fmoles O6 -meG/μg DNA. Of six human breast tumour DNA samples assessed, five had detectable O6-AlkG levels (mean ± SD 1.24 ± 0.25 O6-meG equivalents/μg DNA. This study shows the potential usefulness of the ASB assay to detect and quantify total O6-AlkGs in human DNA samples.

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. • NDMA exposure led to oxidative stress in AGS cells. • NDMA increased Cldn-1 and -6 expression. • NDMA increased Stat3 and ERK2 phosphorylation. • NDMA triggered transcription of pro-inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Berries are known to have disease preventive and anticancer properties. We studied whether supplementing a habitual diet rich in red meat with berries affects cancer biomarkers in a clinical trial with 43 healthy volunteers. We exposed Caco-2 and HCA-7 colon adenocarcinoma cells and HaCaT cells, representing non-cancerous epithelial tissue, in 2D and 3D cultures to faecal water extracted from stool samples collected at baseline and at the end of the 4-wk trial. Expression of markers from the Wnt/β-catenin and PI3K/AKT/mTOR pathways, the cell proliferation marker Ki67, and the apoptosis marker cleaved caspase-3 were detected by Western blotting and immunofluorescence staining methods. In addition, genotoxicity of faecal water and the concentration of N-nitroso compounds in the faeces were analysed. The diet supplemented with berries caused downregulation of β-catenin, PS6 as well as Ki67 signalling in the cells exposed to faecal water. Our results suggest that consuming berries as part of a habitual Western-type diet could lead to less cancerous colon metabolism and possibly lower the risk for colorectal cancer by modulating the central signalling pathways in cancer.

Abstract Background Nitrosatable drugs commonly prescribed during pregnancy can react with nitrite to form N-nitroso compounds which have been associated with an increased risk of stillbirth. Whether maternal residential drinking water nitrate modifies this association is unknown. We investigated, if household drinking water nitrate was associated with stillbirth, and if it modified the association between nitrosatable prescription drug intake and the risk of stillbirth. Methods We conducted an individual-level register- and population-based cohort study using 652,810 women with the first recorded singleton pregnancy in the Danish Medical Birth Registry between 1997 and 2017. Nitrosatable drug exposure was recorded by use of the Danish National Patient Registry defined as women with a first redeemed prescription of a nitrosatable drug the first 22 weeks of pregnancy. The reference group was women with no redeemed prescription of a nitrosatable drug in this period. The average individual drinking water nitrate concentration level (mg/L) was calculated in the same period. We categorized nitrosatable drugs as secondary amines, tertiary amines, and amides. Cox hazard regression was used to estimate crude and adjusted hazard ratios with 95% confidence intervals for stillbirth stratified into five categories of nitrate concentrations: ≤1 mg/L, > 1- ≤ 2 mg/L, > 2- ≤ 5 mg/L, > 5- ≤ 25 mg/L, and > 25 mg/L. Results Drinking water nitrate exposure in the population was not associated with the risk of stillbirth. Among 100,244 women who had a nitrosatable prescription drug redeemed ≤22 weeks of pregnancy of pregnancy, 418 (0.42%) had a stillbirth compared to 1993 stillbirths (0.36%) among 552,566 referent women. Women with any nitrosatable prescription drug intake and > 1- ≤ 2 mg/L nitrate concentration had an increased risk of stillbirth [adjusted hazard ratio 1.55 (95% confidence interval, 1.15–2.09)] compared with referent women. In the stratified analyses, the highest risk of stillbirth was found among women with secondary amine intake and > 25 mg/L nitrate concentrations [adjusted hazard ratio 3.11 (95% CI, 1.08–8.94)]. Conclusions The association between nitrosatable prescription drug intake and the risk of stillbirth may depend on the level of nitrate in household drinking water. Evaluations of the effect of nitrosatable drug intake on perinatal outcomes might consider nitrate exposure from drinking water.

Meat and meat products are important foods in the human diet, but there are concerns about their quality and safety. The discovery of carcinogenic and genotoxic N-nitroso compounds (NOCs) in processed meat products has had serious negative impacts on the meat industry. In order to clarify the relationship between the use of nitrite or nitrate and the safety of meat or meat products, we reviewed NOCs in meat and meat products, the origin and safety implications of NOCs, effects of nitrite and nitrate on meat quality, national regulations, recent publications concerning the using of nitrite and nitrate in meat or meat products, and reduction methods. By comparing and analyzing references, (1) we found antioxidant, flavor improvement and shelf-life extension effects were recently proposed functions of nitrite and nitrate on meat quality, (2) the multiple functions of nitrite and nitrate in meat and meat products couldn't be fully replaced by other food additives at present, (3) we observed that the residual nitrite in raw meat and fried meat products was not well monitored, (4) alternative additives seem to be the most successful methods of replacing nitrite in meat processing, currently. The health risks of consuming processed meat products should be further evaluated, and more effective methods or additives for replacing nitrite or nitrate are needed.

Subsequent to the dietary uptake of nitrate/nitrite in combination with acetaldehyde/ethanol, combination effects resulting from the sustained endogenous exposure to nitrite and acetaldehyde may be expected. This may imply locoregional effects in the upper gastrointestinal tract as well as systemic effects, such as a potential influence on endogenous formation of N-nitroso compounds (NOC). Salivary concentrations of the individual components nitrate and nitrite and acetaldehyde are known to rise after ingestion, absorption and systemic distribution, thereby reflecting their respective plasma kinetics and parallel secretion through the salivary glands as well as the microbial/enzymatic metabolism in the oral cavity. Salivary excretion may also occur with certain drug molecules and food constituents and their metabolites. Therefore, putative combination effects in the oral cavity and the upper digestive tract may occur, but this has remained largely unexplored up to now. In this Guest Editorial, published evidence on exposure levels and biokinetics of nitrate/nitrite/NOx, NOC and acetaldehyde in the organism is reviewed and knowledge gaps concerning combination effects are identified. Research is suggested to be initiated to study the related unresolved issues. [ABSTRACT FROM AUTHOR]

The study of the properties of polymer fibers is an urgent and important task for the creation of new, promising materials and modification of their properties under operating conditions. Using the methods of EPR and IR spectroscopy, thermoanalytical methods, and scanning electron microscopy, a comprehensive study of low-temperature oxidation in the air of poly-p-phenylene terephthalamide (terlon), previously nitrated with nitrogen oxides, and the mechanism of this process is presented. The phenylnitrite fragments of macromolecules formed during nitration are identified as an oxidation initiator. The polymer is destroyed as a result of the decomposition of N-nitrosoamides, N-nitro compounds, and N-nitrites: the products of terlon nitration. The main products of terlon nitration, esters and carboxylic acids, are determined by IR spectroscopy. [ABSTRACT FROM AUTHOR]

Monitoring the prevalence and persistence of N -nitrosamines and their precursors in wastewater treatment plants (WWTPs) and effluent-receiving aquatic compartments is a priority for utilities practicing wastewater recycling or exploiting wastewater-impacted source waters. In this work, we developed an analytical framework that combines liquid chromatography-high-resolution mass spectrometry (LC-HRMS) with acidic triiodide-chemiluminescence analysis to characterize the composition and fate of total N -nitrosamines (TONO) and their precursors along the treatment trains of eight WWTPs in New York. Through the parallel application of LC-HRMS and chemiluminescence methods, the TONO scores for 41 N -nitrosamines containing structurally diverse substituents on their amine nitrogen were derived based on their solid-phase extraction recoveries and conversion efficiencies to nitric oxide. Correcting the compositional analysis of TONO using the TONO scores of target N -nitrosamines refined the assessment of the reduction or accumulation of TONO and their precursors across treatment steps in WWTPs. Nontargeted analysis prioritized seven additional N -nitrosamines for confirmation by reference standards, including three previously uncharacterized species: N -nitroso- tert -butylphenylamine, N -nitroso-2-pyrrolidinmethanol, and N -nitrosodesloratadine, although they only served as minor components of TONO. Overall, our study establishes an adaptable methodological framework for advancing the quantitative and qualitative analysis of specific and unknown components of TONO across water treatment and reuse scenarios.

Diet is one of the main exogenous sources of potentially carcinogenic nitrosamines (NAs) along with tobacco and cosmetics. Several factors can affect endogenous N-nitroso compounds (NOCs) formation and therefore the potential damage of the intestinal mucosa at initial colorectal cancer stages. To address this issue, 49 volunteers were recruited and classified according to histopathological analyses. Lifestyle and dietary information were registered after colonoscopy. The mutagenicity of fecal supernatants was assayed by a modified Ames test. Fecal heme-derived NOCs and total NOC concentrations were determined by selective denitrosation and chemiluminescence-based detection. Results revealed processed meats as the main source of dietary nitrites and NAs, identifying some of them as predictors of the fecal concentration of heme-derived and total NOCs. Furthermore, increased fecal NOC concentrations were found as the severity of colonic mucosal damage increased from the control to the adenocarcinoma group, these concentrations being strongly correlated with the intake of the NAs N-nitrosodimethylamine, N-nitrosopiperidine, and N-nitrosopyrrolidine. Higher fecal NOC concentrations were also noted in higher fecal mutagenicity samples. These results could contribute to a better understanding of the importance of modulating dietary derived xenobiotics as related with their impact on the intestinal environment and colonic mucosa damage.

Background: Nitrosatable drugs commonly prescribed during pregnancy can react with nitrite to form N-nitroso compounds which have been associated with an increased risk of stillbirth. Whether maternal residential drinking water nitrate modifies this association is unknown. We investigated, if household drinking water nitrate was associated with stillbirth, and if it modified the association between nitrosatable prescription drug intake and the risk of stillbirth.Methods: We conducted an individual-level register- and population-based cohort study using 652,810 women with the first recorded singleton pregnancy in the Danish Medical Birth Registry between 1997 and 2017. Nitrosatable drug exposure was recorded by use of the Danish National Patient Registry defined as women with a first redeemed prescription of a nitrosatable drug the first 22 weeks of pregnancy. The reference group was women with no redeemed prescription of a nitrosatable drug in this period. The average individual drinking water nitrate concentration level (mg/L) was calculated in the same period. We categorized nitrosatable drugs as secondary amines, tertiary amines, and amides. Cox hazard regression was used to estimate crude and adjusted hazard ratios with 95% confidence intervals for stillbirth stratified into five categories of nitrate concentrations: ≤1 mg/L, > 1- ≤ 2 mg/L, > 2- ≤ 5 mg/L, > 5- ≤ 25 mg/L, and > 25 mg/L.Results: Drinking water nitrate exposure in the population was not associated with the risk of stillbirth. Among 100,244 women who had a nitrosatable prescription drug redeemed ≤22 weeks of pregnancy of pregnancy, 418 (0.42%) had a stillbirth compared to 1993 stillbirths (0.36%) among 552,566 referent women. Women with any nitrosatable prescription drug intake and > 1- ≤ 2 mg/L nitrate concentration had an increased risk of stillbirth [adjusted hazard ratio 1.55 (95% confidence interval, 1.15-2.09)] compared with referent women. In the stratified analyses, the highest risk of stillbirth was found among women with secondary amine intake and > 25 mg/L nitrate concentrations [adjusted hazard ratio 3.11 (95% CI, 1.08-8.94)].Conclusions: The association between nitrosatable prescription drug intake and the risk of stillbirth may depend on the level of nitrate in household drinking water. Evaluations of the effect of nitrosatable drug intake on perinatal outcomes might consider nitrate exposure from drinking water. [ABSTRACT FROM AUTHOR]

Copyright of Shipin Kexue/ Food Science is the property of Food Science Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Nitroso chemistry has gained considerable interest in the fields of chemistry and biology over the past few decades. Over the years, synthetic methods to prepare a diverse range of N -nitrosamide derivatives using different nitrosating agents have been developed. Further, these nitrosamides have been utilized for the preparation of structurally significant compounds. [Display omitted] Nitroso chemistry has gained considerable interest in the fields of chemistry and biology over the past few decades. However, while N -nitrosamines and C -nitrosamines have been extensively studied, N -nitrosamides have received relatively less attention in the literature. In recent years, various synthetic chemists have developed dynamic synthetic approaches to prepare a diverse range of N -nitrosamide derivatives using different nitrosating agents. Further, these nitrosamides have been utilized for the preparation of structurally significant compounds such as amides, esters, thioesters, acids, alcohols, acyl hydrazides, glycouronamides, and heterocycles like indazole scaffolds through transamidation, esterification, thioesterification, reduction and aryne σ-insertion followed by C(sp3)–H bond functionalization strategy under suitable reaction conditions. Moreover, synthesis of other nitrosamides such as nitrosocarbamates, nitrosoureas and nitrososultams is also described. In this brief review, we highlight the progress in this field, focusing on the synthesis and applications of N -nitrosamides in various organic transformations. Moreover, the reaction mechanisms have also been included for the respective reactions. The contents of the review include the following subsections. [ABSTRACT FROM AUTHOR]

Abstract Background Nitrate is converted to nitrite in the human body and subsequently can react with amines and amides in the gastrointestinal tract to form N-nitroso compounds (NOCs), which are known to be carcinogenic in animals. Humans can be exposed to nitrate via consumption of drinking water and diet, especially green leafy vegetables and cured meat. The contribution of nitrate from drinking water in combination with meat intake has not been investigated thoroughly. Therefore, in the present pilot study, we examined the effect of nitrate from drinking water, and its interaction with the consumption of white and processed red meat, on the endogenous formation of NOCs, taking into account the intake of vitamin C, a nitrosation inhibitor. Methods Twenty healthy subjects were randomly assigned to two groups consuming either 3.75 g/kg body weight (maximum 300 g per day) processed red meat or unprocessed white meat per day for two weeks. Drinking water nitrate levels were kept low during the first week (

N-nitroso compounds (NOC) are produced by the acid catalyzed reaction of nitrite with certain nitrogen compounds. The gastrointestinal tract (GI) is the main site for the formation of reactive nitrogen species (RNS). Bacteria present on the GI tract surface reduced the dietary nitrate or nitrite into Nitric oxide NO and other related compounds. The clinical sign of NOC carcinogenicity varies according to species, dose, and route of administration. Humans are exposed to preformed N-nitroso compounds and endogenous NOC via the environmental food chain. Several NOC are potential human carcinogens, including DENA and NDMA, but evidence from population studies is inconsistent.

Background: High dietary intake of nitrate and nitrite might increase the risk of type 1 diabetes. To our knowledge, no earlier prospective study has explored whether maternal dietary intake of nitrate and nitrite during pregnancy is associated with the risk of type 1 diabetes in the offspring.Objective: Our aim was to study association between maternal intake of nitrate and nitrite during pregnancy and the risk of islet autoimmunity and type 1 diabetes in the offspring.Design: Children born between 1997 and 2004 at Oulu and Tampere University Hospitals in Finland and carrying increased human leukocyte antigen (HLA)-conferred risk for type 1 diabetes were followed in the Type 1 Diabetes Prediction and Prevention (DIPP) study from 3 mo of age. Islet autoantibodies were screened at 3- to 12-mo intervals from serum samples. Of 4879 children, 312 developed islet autoimmunity and 178 developed type 1 diabetes during a 15-y follow-up. Maternal intake of nitrate and nitrite during the eighth month of pregnancy was assessed after birth using a validated self-administered FFQ. Cox proportional hazards regression was used for the statistical analyses.Results: Maternal intake of nitrate and nitrite during pregnancy was not associated with the child's risk of islet autoimmunity [nitrate: HR 0.99 (95% CI: 0.88, 1.11); nitrite: HR 1.03 (95% CI: 0.92, 1.15)] or type 1 diabetes [nitrate: HR 1.02 (95% CI: 0.88, 1.17); nitrite: HR 0.97 (95% CI: 0.83, 1.12)] when adjusted for energy (residual method), sex, HLA risk group, and family history of diabetes. Further adjustment for dietary antioxidants (vitamin C, vitamin E, and selenium) did not change the results.Conclusion: Maternal dietary intake of nitrate or nitrite during pregnancy is not associated with the risk of islet autoimmunity or type 1 diabetes in the offspring genetically at risk for type 1 diabetes. [ABSTRACT FROM AUTHOR]

N-nitroso compounds (NOC) are produced by the acid catalyzed reaction of nitrite with certain nitrogen compounds. The gastrointestinal tract (GI) is the main site for the formation of reactive nitrogen species (RNS). Bacteria present on the GI tract surface reduced the dietary nitrate or nitrite into Nitric oxide (NO) and other related compounds. The clinical sign of NOC carcinogenicity varies according to species, dose, and route of administration. Humans are exposed to preformed N-nitroso compounds and endogenous NOC via the environmental food chain. Several NOC are potential human carcinogens, including DENA and NDMA, but evidence from population studies is inconsistent. [ABSTRACT FROM AUTHOR]

Beetroot juice (BRJ) has become increasingly popular amongst athletes aiming to improve sport performances. BRJ contains high concentrations of nitrate, which can be converted into nitric oxide (NO) after consumption. NO has various functions in the human body, including a vasodilatory effect, which reduces blood pressure and increases oxygen- and nutrient delivery to various organs. These effects indicate that BRJ may have relevant applications in prevention and treatment of cardiovascular disease. Furthermore, the consumption of BRJ also has an impact on oxygen delivery to skeletal muscles, muscle efficiency, tolerance and endurance and may thus have a positive impact on sports performances. Aside from the beneficial aspects of BRJ consumption, there may also be potential health risks. Drinking BRJ may easily increase nitrate intake above the acceptable daily intake, which is known to stimulate the endogenous formation of N-nitroso compounds (NOC's), a class of compounds that is known to be carcinogenic and that may also induce several other adverse effects. Compared to studies on the beneficial effects, the amount of data and literature on the negative effects of BRJ is rather limited, and should be increased in order to perform a balanced risk assessment. [ABSTRACT FROM AUTHOR]

The health safety of beer is still a discussed topic. In the Czech Republic, there is a well-developed system for controlling the content of potential beer contaminants, which are regularly attended by a number of large and medium-sized breweries and are organized by laboratories of the Research Institute of Brewing and Malting. For many years aliphatic chlorinated hydrocarbons, biogenic amines, nitrates, phthalates, ATNC, nitrosamines, polychlorinated biphenyls, polycyclic aromatic hydrocarbons, heavy metals, mycotoxins, coliforms, and recently pesticides in beer have been analyzed. This study summarizes five-year results and extends information about the origin, health risks and hygiene limits of controlled substances and bacteria in beer. The study proves that the level of health safety of beers in the Czech Republic is very high, which is closely related to the high hygiene level of controlled breweries. The number of positive samples was only minor, 8 positive samples were found in 220 beer samples controlled for 44 chemical contaminants. Three positive samples contaminated by coliform bacteria were found among 675 controlled ones.

Heme iron overload has been implicated as the main cause of the increased risk of cancer due to the consumption of red meat. However, fish and shellfish, teas, and spices contain up to five times more iron than red meat. There is insufficient evidence that iron intake in dietary red meat is the primary causal factor for colorectal cancer. In addition, harmful substances produced during the preparation of red meat, including heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs), N‐nitroso compounds, and acrylamide, are extrinsic factors that increase carcinogenicity. HCAs are produced during the cooking of red meat, poultry meat, and fish. PAHs may also be produced during the cooking of diverse food groups, such as dairy products, fruits, vegetables, and cereals. The average daily intake of red meat among Korean individuals is 62 g; the amount of PAHs entering the body via red meat is less than the average amount of PAHs the body is exposed to in the air. Therefore, it is difficult to conclude that dietary red meat is the main cause of colorectal cancer. Rather, there may be an intricate influence of multiple factors, including fruit and vegetable intake, alcohol consumption, smoking, overweight, obesity, and stress. [ABSTRACT FROM AUTHOR]

• A Quick Easy Cheap Effective Rugged Safe (QuEChERS) method resulted in best analyte recoveries. • Recovery efficiencies exceeded 89% for most target analytes in serum and urine. • Most analytes showed minimal matrix effects (between 80 and 120%) in both matrices. • QuEChERS is an advantageous alternative for pesticide analysis in serum and urine. 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 (MgSO 4) and 50 mg sodium acetate were added for serum and 200 mg MgSO 4 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. [ABSTRACT FROM AUTHOR]

This review article aims to provide a comprehensive overview of recent epidemiology, pathogenesis, risk factors, and premalignant conditions of gastric cancer. Worldwide, gastric cancer is one of the most common and most fatal cancers. The incidence and mortality remain high in regions such as East Asia and Eastern Europe. Although there is a lower incidence in the United States, it remains a deadly disease. Age, gender, and race are non-modifiable demographic risk factors for developing gastric cancer. There have been several dietary and lifestyle risk factors such as salt preserved foods, N-nitroso compounds containing foods, tobacco smoke, alcohol use, and obesity that have been shown to contribute to the development of gastric cancer. Infections have additionally been shown to have a clear role in the pathogenesis of gastric cancer as Helicobacter pylori eradication has shown a significant reduction in the incidence of gastric cancer as well as other pathogens such as Epstein-Barr virus. There are certain premalignant lesions that increase the risk of developing gastric cancer. These include atrophic gastritis, and intestinal metaplasia amongst others., Competing Interests: Conflicts of interest: The authors declared no potential conflicts of interest with respect to the research, authorship, and publication of this article., (© 2023 Greater Baltimore Medical Center.)

N-nitroso compounds (NOCs) exposure is a major risk factor for the development of gastric cancer. However, the carcinogenic mechanisms by which NOCs induce gastric and other cancers, especially the NOCs-induced Warburg effect, have not been comprehensively studied. Lactate dehydrogenase (LDH), which has two subunits (LDHA and LDHB), plays an important role in the Warburg effect of tumor cells. Therefore, we hypothesized that LDHA and LDHB could promote Warburg effect in malignant transformed GES-1 cells induced by Nmethyl-N′-nitro-N-nitrosoguanidine (MNNG). GES-1 cells were exposed to 1 μmol/L MNNG and cultured for 40 passages. During the culturing process, cell proliferation, migration, and soft agar colony formation significantly increased after 30 passages. Following MNNG exposure, lactate, LDH, glucose uptake, and the expression levels of key enzymes in glycolysis were significantly increased. Knocking down LDHA or LDHB alone reduced lactate secretion, inhibited cell viability, and impaired migratory capacities. Knocking down LDHA and LDHB together fully suppressed lactate secretion and effectively suppressed the malignant phenotype of cells transformed by long-term MNNG exposure. Finally, we demonstrated that overexpression of LDHA and LDHB promotes the malignant transformation of GES-1 cells by enhancing the Warburg effect during long-term exposure to NOCs. • Long-tern MNNG exposure induced Warburg effect in GES-1 cells. • Both expression of LDHA and LDHB was increased in transformed GES-1 cells by MNNG. • LDHA and LDHB play an important role in Warburg effect of transformed GES-1 cells by MNNG. • MNNG have the potential binding sites with LDHA and LDHB. [ABSTRACT FROM AUTHOR]

Farmers occasionally need to add nitrogen fertilizer to their farms and gardens to make available just the precise nutrients for their plants' growth. The applications of inorganic nitrogen fertilizers to various crops have been continuously increasing since last many decades globally. Although nitrogen fertilizer contributes substantially to yield enhancement, but excessive use of this manure has posed serious threats to environment and human health. Rate of nitrogen fertilizers application has a close relationship with nitrate accumulation in surrounding environment, groundwater, as well as leafy and root vegetables. Consumption of diets having high nitrate contents has contributed to endogenous nitrosation, which could lead to thyroid condition, various kinds of human cancers, neural tube defects (during fetus development), and diabetes. In this short review, the authors have tried to create awareness among general public, farming community, health practitioners, and agricultural scientists for the risk involved with excessive use of nitrogen fertilizers to human health. Carcinogenic activity and other adverse effects of N-nitroso compounds might be prevented by consuming vitamin C and antioxidants containing fruits and vegetables. [ABSTRACT FROM AUTHOR]

Meat products can be contaminated with carcinogenic N-nitrosamines, which is ascribed to the reaction between a nitrosating agent, originating from nitrite or smoke, and a secondary amine, derived from protein and lipid degradation. Although in model systems it is demonstrated that many amine containing compounds can be converted to N-nitrosamines, the yield is dependent of reaction conditions (e.g., low pH and high temperature). In this article, the influence of the composition of the meat products (e.g., pH, aw, spices) and processing (e.g., ageing, ripening, fermentation, smoking, heat treatment and storage) on the presence and availability of the amine precursors and the N-nitrosamine formation mechanism is discussed. In addition, this article explores the current N-nitrosamine mitigation strategies in order to obtain healthier and more natural meat products. [ABSTRACT FROM AUTHOR]

Red meat is consumed globally and plays an important role in the Western diet. Its consumption is however linked with various types of diseases. This review focuses on the relationship of red meat with cancer, its dependency on the thermal processing methodology and the subsequent physiological effects. The epidemiological evidence is discussed, followed by introduction of the species that were hypothesized to contribute to these carcinogenic effects including polycyclic aromatic hydrocarbons (PAHs), heterocyclic amines (HCAs), N-nitroso compounds (NOCs), heme iron, and macromolecular oxidation products. Their carcinogenic mechanisms were then addressed with further emphasis on the involvement of inflammation and oxidative stress. The thermal processing dependency of the carcinogen generation and the partially elucidated carcinogenic mechanism both represent doorways of opportunities available for the scientific manipulation of their impact after human consumption, to minimize the cancer risks associated with red meat. [ABSTRACT FROM AUTHOR]

Nitrosamine impurities in pharmaceuticals have recently been concerned for several national regulatory agencies to avoid carcinogenic and mutagenic effects in patients. The demand for highly sensitive and specific analytical methods with LOQs in the ppb and sub-ppb ranges is among the most significant challenges facing analytical scientists. In addition, artifactual nitrosamine formation during sample preparation and injection leading to overestimation of nitrosamines has received considerable attention. Numerous analytical methodologies have been reported for quantifying nitrosamine impurities in active pharmaceutical ingredients and medicinal products at the interim limit criteria as preventive measures. In this review, we meticulously discuss those reported gas and liquid chromatographic methods for nitrosamine determination in pharmaceuticals in aspects of chromatographic conditions and sensitivity of detection. We also introduce the potential of novel fluorescence-based methods recently developed to rapidly screen nitrosamine impurities. In addition, the review assesses the nitrosation assay procedure (NAP test), which is expected to be a future preventive measure for screening potential nitrosation and identifying suspected contamination with N -nitroso or other potential mutagenic impurities during the drug development process. [Display omitted] • The chromatographic-based methodologies for nitrosamine determination are reviewed. • Artifactual and isobaric interferences leading to overestimation or false positive results are addressed. • Fluorescence-based methods for rapid and specific quantification of nitrosamines in pharmaceuticals are discussed. • Screening and identifying nitrosamines during drug development via the Nitrosation Assay Procedure are discussed. [ABSTRACT FROM AUTHOR]

[Display omitted] • β-catenin expression is downregulated in diet supplemented with berries. • Cell proliferation is downregulated in women following Meat&Berries diet. • Genotoxicity of faecal water is attenuated in Meat&Berries diet. • N -nitroso compound formation is unaffected by supplementating berries to the diet. Berries are known to have disease preventive and anticancer properties. We studied whether supplementing a habitual diet rich in red meat with berries affects cancer biomarkers in a clinical trial with 43 healthy volunteers. We exposed Caco-2 and HCA-7 colon adenocarcinoma cells and HaCaT cells, representing non-cancerous epithelial tissue, in 2D and 3D cultures to faecal water extracted from stool samples collected at baseline and at the end of the 4-wk trial. Expression of markers from the Wnt/β-catenin and PI3K/AKT/mTOR pathways, the cell proliferation marker Ki67, and the apoptosis marker cleaved caspase-3 were detected by Western blotting and immunofluorescence staining methods. In addition, genotoxicity of faecal water and the concentration of N -nitroso compounds in the faeces were analysed. The diet supplemented with berries caused downregulation of β-catenin, PS6 as well as Ki67 signalling in the cells exposed to faecal water. Our results suggest that consuming berries as part of a habitual Western-type diet could lead to less cancerous colon metabolism and possibly lower the risk for colorectal cancer by modulating the central signalling pathways in cancer. [ABSTRACT FROM AUTHOR]

N -Nitrosamines form as byproducts during oxidative water treatment and occur as impurities in consumer and industrial products. To date, two methods based on chemiluminescence (CL) detection of nitric oxide liberated from N -nitrosamines via denitrosation with acidic triiodide (HI 3 ) treatment or ultraviolet (UV) photolysis have been developed to enable the quantification of total N -nitrosamines (TONO) in environmental water samples. In this work, we configured an integrated experimental setup to compare the performance of HI 3 -CL and UV-CL methods with a focus on their applicability for TONO measurements in wastewater samples. With the use of a large-volume purge vessel for chemical denitrosation, the HI 3 -CL method achieved signal stability and detection limits comparable to those achieved by the UV-CL method which utilized a microphotochemical reactor for photolytic denitrosation. Sixty-six structurally diverse N -nitroso compounds (NOCs) yielded a range of conversion efficiencies relative to N -nitrosodimethylamine (NDMA) regardless of the conditions applied for denitrosation. On average, TONO measured in preconcentrated raw and chloraminated wastewater samples by the HI 3 -CL method were 2.1 ± 1.1 times those measured by the UV-CL method, pointing to potential matrix interferences as further confirmed by spike recovery tests. Overall, our comparative assessment of the HI 3 -CL and UV-CL methods serves as a basis for addressing methodological gaps in TONO analysis.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the world. The vast majority of CRC cases have been linked to environmental causes rather than to heritable genetic changes. Over the last decades, epidemiological evidence linking the consumption of red and, more convincingly, of processed red meat to CRC has accumulated. In parallel, hypotheses on carcinogenic mechanisms underlying an association between CRC and the intake of red and processed red meat have been proposed and investigated in biological studies. The hypotheses that have received most attention until now include (1) the presence of polycyclic aromatic hydrocarbons and heterocyclic aromatic amines, two groups of compounds recognized as carcinogenic, (2) the enhancing effect of (nitrosyl)heme on the formation of carcinogenic N-nitroso compounds and lipid peroxidation. However, none of these hypotheses completely explains the link between red and processed red meat intake and the CRC risk. Consequently, scientists have proposed additional mechanisms or refined their hypotheses. This review first briefly summarizes the development of CRC followed by an in-depth overview and critical discussion of the different potential carcinogenic mechanisms underlying the increased CRC risk associated with the consumption of red and processed red meat. [ABSTRACT FROM PUBLISHER]

Epidemiology and experimental studies provide an overwhelming support of the notion that diets high in red or processed meat accompany an elevated risk of developing pre-neoplastic colorectal adenoma and frank colorectal carcinoma (CRC). The underlying mechanisms are disputed; thus several hypotheses have been proposed. A large body of reports converges, however, on haem and nitrosyl haem as major contributors to the CRC development, presumably acting through various mechanisms. Apart from a potentially higher intestinal mutagenic load among consumers on a diet rich in red/processed meat, other mechanisms involving subtle interference with colorectal stem/progenitor cell survival or maturation are likewise at play. From an overarching perspective, suggested candidate mechanisms for red/processed meat-induced CRC appear as three partly overlapping tenets: (i) increased N-nitrosation/oxidative load leading to DNA adducts and lipid peroxidation in the intestinal epithelium, (ii) proliferative stimulation of the epithelium through haem or food-derived metabolites that either act directly or subsequent to conversion, and (iii) higher inflammatory response, which may trigger a wide cascade of pro-malignant processes. In this review, we summarize and discuss major findings of the area in the context of potentially pertinent mechanisms underlying the above-mentioned association between consumption of red/processed meat and increased risk of developing CRC. [ABSTRACT FROM AUTHOR]

Nitrosamines occur widespread in food, drinking water, cosmetics, as well as tobacco smoke and can arise endogenously. More recently, nitrosamines have been detected as impurities in various drugs. This is of particular concern as nitrosamines are alkylating agents that are genotoxic and carcinogenic. We first summarize the current knowledge on the different sources and chemical nature of alkylating agents with a focus on relevant nitrosamines. Subsequently, we present the major DNA alkylation adducts induced by nitrosamines upon their metabolic activation by CYP450 monooxygenases. We then describe the DNA repair pathways engaged by the various DNA alkylation adducts, which include base excision repair, direct damage reversal by MGMT and ALKBH, as well as nucleotide excision repair. Their roles in the protection against the genotoxic and carcinogenic effects of nitrosamines are highlighted. Finally, we address DNA translesion synthesis as a DNA damage tolerance mechanism relevant to DNA alkylation adducts.

Various drug samples (N = 249; drug substances, tablets, capsules, solutions, crèmes, and more) from the European pharmaceutical market were collected since 2019 and analyzed for 16 nitrosamines (NAs). In 2.0% of the cases, NAs were detected. These findings included four active pharmaceutical ingredients already known for potential NA contamination: losartan (N-nitrosodimethylamine [NDMA] and N-nitrosodiethylamine, simultaneously), valsartan (NDMA), metformin (NDMA) and ranitidine (NDMA). The fifth new finding, which has not been reported yet, discovered contamination of a molsidomine tablet sample with N-nitrosomorpholine (NMor). The tablet contained 144% of the toxicological allowable intake for NMor. NMor was included in our screening from the beginning and is currently the focus of regulatory authorities, but was added to the guidelines only last year. Thus, it may not have been the focus of regulatory investigations for too long. Our results indicate that the majority of drug products in the market are nonhazardous in terms of patient safety and drug purity. Unfortunately, the list of individual affected products keeps growing constantly and new NA cases, such as molsidomine or nitrosated drug substances (nitrosamine drug substance-related impurities [NDSRI]), continue to emerge. We therefore expect nitrosamine screenings to remain a high priority., (© 2022 The Authors. Archiv der Pharmazie published by Wiley-VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.)