Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Nitroso Compounds”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 883 records · Page 49Linked to original sources
PubMed1995

Potential genotoxicity of chronically elevated nitric oxide: a review.

Several human cancers are associated with chronic bacterial, viral and parasitic infections. Nitric oxide, which is a short-lived free radical produced by many types of cells for a number of important physiological functions, is elevated in these infections. Long-term exposure to elevated NO. in cells could have potential genotoxic effects on hosts. There are at least three mechanisms by which intracellular elevated NO. could exert genotoxic affects after reacting with O2. These include formation of carcinogenic N-nitroso compounds, direct deamination of DNA bases, and oxidation of DNA after formation of peroxynitrite and/or hydroxyl radicals. One or more of these mechanisms could, theoretically, explain why chronic infection increases the risk of certain cancers.

Animals↗
PubMed1991

Bacterial N-nitrosation and gastric carcinogenesis in humans.

It has been hypothesized that bacterially produced N-nitroso compounds cause the progression from chronic atrophic gastritis through intestinal metaplasia and dysplasia to gastric cancer. If this is true then various consequences follow. These consequences are discussed, together with the evidence for or against them. The conclusion is that there is much to support the hypothesis.

Bacterial Physiological Phenomena↗
PubMed2005

Development of a food frequency questionnaire module and databases for compounds in cooked and processed meats.

There is ample evidence from basic research and animal carcinogenicity studies that heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) are mutagens and carcinogens. However, there was a paucity of human data due to a lack of appropriate investigative tools. We developed the first validated cooked meat module within a food frequency questionnaire (FFQ) in the United States of America and created databases to be used in conjunction with this FFQ to estimate intake of HCAs and benzo[a]pyrene, a marker of PAHs. It became clear that other aspects of meat may also contribute to carcinogenesis; in particular, we are pursuing two additional areas: processed meat and iron exposure in relation to cancer risk. To investigate these hypotheses, we have expanded the cooked meat module to include detailed information on processed meats and fish. In addition, we are developing two databases, one for total iron and heme iron in cooked meat and the other for nitrite, nitrate, and N-nitroso compounds in processed meats. In this report, we will outline the methods used to develop the meat questionnaires, the databases, a software package for generating the intake values, and the methods used to generate nutritional data from nationally representative samples.

Benzo(a)pyrene↗
PubMed1982

Effect of ozonation on the mutagenicity of carcinogens in aqueous solution.

Ozone is a very strong oxidizing agent that may be used in water purification. The effect of ozonation on the mutagenicity of mutagens and/or carcinogens of diverse chemical structures was evaluated as measured by the Salmonella/microsome assay. The effect of ozonation of 36 mutagens and/or carcinogens has been evaluated and the results of 15 reported here. The mutagenicity of polycyclic aromatic hydrocarbons and aromatic amines was inactivated by ozone treatment, while alkylating agents, nitro aromatics, and nitroso compounds were not affected. Ozonation of hydrazines produced mutagenic intermediates that may be susceptible to base-catalyzed hydrolysis. Therefore, depending on the chemical present, ozonation may be useful in the treatment of waters containing organic carcinogens, including drinking water, waste-water effluents, and other aqueous waste materials containing carcinogens.

Alkylating Agents↗
PubMed1981

Gastritis, nitrosamines, and gastric cancer.

Gastritis is associated with peptic ulcer, gastroenterostomy, pernicious anemia, and exposure to nitrosamines. Once established, the process may be self-perpetuating, resulting in atrophy, metaplasia, dysplasia, and neoplasia. This can be explained by the process of endogenous nitrosation of amines in the inflamed gastric mucosa. Evidence is presented to support this hypothesis. Several drugs given parenterally have been identified as mutagenic nitroso compounds in homogenates of human and canine antral mucosa. Nitrite for this process is apparently derived from the inflamed mucosa. Different amines appear to be nitrosated at different places in the antrum, suggesting the presence of site-specific enzymes that control these reactions.

Animals↗
PubMed1984

Detoxification of nitrosamides and nitrosocarbamates in blood plasma and tissue homogenates.

Nitrosamides and nitrosocarbamates exhibit relatively high mutagenic activity in Salmonella when compared with nitrosoureas. This high activity can be accounted for by activation of nitrosamides and nitrosocarbamates by cellular thiols, predominantly reduced glutathione, that are present intracellularly at concentrations in the millimolar range. In striking contrast to the in vitro mutagenicity tests, a number of studies have indicated that nitrosamides and nitrosocarbamates are less potent than nitrosoureas when tested in vivo in model systems such as the mouse. We extend here previous studies [Aukerman et al, 1983] that demonstrate striking chemical decomposition and inactivation of mutagenic activity of nitrosamides and nitrosocarbamates during exposure to murine blood plasma. Plasma glutathione concentrations are inadequate to account for the rapid inactivations noted. Furthermore, the predominant inactivating species is heat-sensitive, nondialyzable, and is greater than 25,000 daltons in size as judged by ultrafiltration experiments. Serum albumin has some inactivating capacity at the concentration found in undiluted plasma and could account for the very low but significant inactivating capacity of human plasma. On the other hand, serum albumin lacks the potency necessary to account for the extremely high levels of inactivating activity observed in rodent and rabbit plasma. Elsewhere we present evidence that carboxylesterase activity is the predominant inactivating species in mouse plasma [Aukerman et al, 1983; Aukerman, 1983; Brundrett and Aukerman, 1984]. Mouse liver, large intestine, kidney, and stomach have more activity per milligram protein under the assay conditions used than plasma itself. Rat liver S9 is also active at enhancing the decomposition of nitrosamides and nitrosocarbamates; most of this inactivating capacity resides in the microsomal fraction. The relatively rapid detoxification of these N-nitroso compounds by plasma and other tissues of rodents has important implications regarding the utility of rodents in assessment of tumorigenicity and/or antitumor activity of these classes of drugs in other animal species. Tests with Salmonella may be of use in estimating relative levels of protection that vary widely among mammalian species.

Animals↗
PubMed1997

The chemistry of perfluoroisobutylene (PFIB) with nitrone and nitroso spin traps: an EPR/Spin trapping study.

While applying electron paramagnetic resonance (EPR)/Spin Trapping techniques, several reactive intermediate species were identified in the reaction of perfluoroisobutylene (PFIB) with nitrone and nitroso spin trap agents: the carbon dioxide radical anion (CO2.-), a carbonyl fluoride intermediate (COF), and vinyl carbanions of PFIB. The reaction of PFIB with N-t-butyl-alpha-phenylnitrone (PBN) forms a dipolar ion which undergoes electron transfer reactions generating stable nitrone spin adducts. Nitroso compounds reacted with carbanions derived from PFIB, which raises the possibility that electron transfer reactions of this type might account for the observed nitroxides. Our results suggest that PFIB undergoes some type of electron transfer reaction leading to several reactive intermediate species (RIS). The implications of these observations on pulmonary damage caused by inhalation of PFIB are discussed.

Electron Spin Resonance Spectroscopy↗
PubMed2006

Grignard reagent-mediated conversion of an acyl nitroso-anthracene cycloadduct to a nitrone.

An intramolecular hetero-Diels-Alder cycloadduct of an acyl nitroso compound and a 9,10-dimethyl anthracene derivative was prepared as a potential nitroxyl (HNO) donor. This compound did not release HNO under any of the conditions tested. Treatment of this cycloadduct with excess MeMgCl resulted in the formation of a nitrone, whose structure was confirmed by X-ray crystallography. A mechanism where MeMgCl acts as a nucleophile, strong base, and Lewis acid possibly explains the formation of this product.

Anthracenes↗
PubMed1991

Endogenous N-nitrosation and cancer of the biliary tract.

Evidence is presented that N-nitroso compounds occur in bile from patients who have undergone surgery for gallstones or had gastrectomy and from unoperated persons. It is unlikely, therefore, that local formation of nitrosamines can account for the excess risk for gallbladder cancer in the first two groups. Gastric formation remains the likeliest hypothesis.

Bile↗
PubMed1979

Role of bacteria in human carcinogenesis.

The bacterial hydrolysis of conjugated carcinogens, production of potential carcinogens from amino acid metabolism, formation of N-nitroso-compounds, and production of carcinogens from bile salt metabolism are discussed. The limited evidence implicating these compounds in the causation of bowel, gastric, bladder, biliary tract and cervical cancer is presented. Although there is no example of a proven role for bacteria in the causation of any human cancer, there are many leads currently under investigation. They have exciting implications for prevention.

Amino Acids↗
PubMed2005

Pharmacokinetics of 1-nitrosomelatonin and detection by EPR using iron dithiocarbamate complex in mice.

The N-nitroso-derivative of melatonin, NOM (1-nitrosomelatonin), which has been demonstrated to be a NO* [oxidonitrogen*] donor in buffered solutions, is a new potential drug particularly in neurological diseases. The advantage of NOM, a very lipophilic drug, is its ability to release both melatonin and NO*, an easily diffusible free radical. In order to evaluate the distribution and the pharmacokinetics of NOM, [O-methyl-3H]NOM was administered to and followed in mice. A complementary method for monitoring NOM, EPR, was performed in vitro and ex vivo with (MGD)2-Fe2+ (iron-N-methyl-D-glucamine dithiocarbamate) complex as a spin trap. The behaviour of NOM was compared with that of GSNO (S-nitrosoglutathione), a hydrophilic NO* donor. In the first minutes following [O-methyl-3H]NOM intraperitoneal injection, the radioactivity was found in organs (6% in the liver, 1% in the kidney and 0.6% in the brain), but not in the blood. In both liver and brain, the radioactivity content decreased over time with similar kinetics reflecting the diffusion and metabolism of NOM and of its metabolites. Based on the characterization and the quantification of the EPR signal in vitro with NOM or GSNO using (MGD)2-Fe2+ complex in phosphate-buffered solutions, the detection of these nitroso compounds was realized ex vivo in mouse tissue extracts. (MGD)2-Fe2+-NO was observed in the brain of NOM-treated mice in the first 10 min following injection, revealing that NOM was able to cross the blood-brain barrier, while GSNO was not.

Animals↗
PubMed1978

[Modern analytical methods and drug safety (author's transl)].

With the N-nitroso compounds for an example this paper tries to show the problems we are confronted with by the commonly admired perfection of modern analytical techniques. By the very same example, however, it can be illustrated how we retreat to decisions ut aliquid fieri videatur if we cannot really master those problems. This seems particularly so when problems of drug safety are at issue.

Carcinogens↗
PubMed2004

Thioproline inhibits development of esophageal adenocarcinoma induced by gastroduodenal reflux in rats.

Several epidemiological cohort studies have suggested that duodeno-gastroesophageal reflux per se induces Barrett's esophagus leading to increased risk of the development of esophageal adenocarcinoma (EAC). However, the exact causative factors behind EAC remain unclear. Recently, we designed a new duodenal contents reflux model which retained normal stomach function. In this model, duodenal contents flowed back into the esophagus and stomach resulting in repeated re-entry into the esophagus through the site of esophagojejunostomy. To elucidate the factors underlying the development of EAC, thiazolidine-4-carboxylic acid (thioproline, TPRO) was applied to the new reflux models as a nitrite scavenger and as a probe to detect reactive nitrogen species (RNS). Post-operatively, 31 animals were divided into two groups according to diet. Animals belonging to the control group were given normal diet (n = 18), while the TPRO group was given food containing 0.5% TPRO (n = 13). All esophageal sections in both groups were examined using hematoxylin and eosin staining and immunohistochemical analysis of inducible nitric oxide synthase (iNOS). EACs developed in 7 of 18 rats (38.9%) of the control group, whereas no EACs were detected in the TPRO group (Fisher's exact test, P < 0.05). Conversely, esophageal squamous cell carcinoma (ESCC) was detected in 1 of 18 rats (5.6%) of the control group and in 1 of 13 rats (7.7%) of the TPRO group. The incidence of ESCC was not significantly different between the two groups (P = 0.671). iNOS protein was overexpressed in Barrett's esophagus of both groups. The present results suggest that RNS such as nitric oxide and peroxynitrite and nitroso compounds derived from reflux of duodenal contents play an important role in the development of EAC, and that the primary causes of ESCC and EAC may differ.

Adenocarcinoma↗
PubMed2002

Concomitant presence of N-nitroso and S-nitroso proteins in human plasma.

Nitric oxide (NO)-mediated nitrosation reactions are involved in cell signaling and pathology. Recent efforts have focused on elucidating the role of S-nitrosothiols (RSNO) in different biological systems, including human plasma, where they are believed to represent a transport and buffer system that controls intercellular NO exchange. Although RSNOs have been implicated in cardiovascular disease processes, it is yet unclear what their true physiological concentration is, whether a change in plasma concentration is causally related to the underlying pathology or purely epiphenomenological, and to what extent other nitrosyl adducts may be formed under the same conditions. Therefore, using gas phase chemiluminescence and liquid chromatography we sought to quantify the basal plasma levels of NO-related metabolites in 18 healthy volunteers. We find that in addition to the oxidative products of NO metabolism, nitrite (0.20 +/- 0.02 micromol/l nitrite) and nitrate (14.4 +/- 1.7 micromol/l), on average human plasma contains an approximately 5-fold higher concentration of N-nitroso species (32.3 +/- 5.0 nmol/l) than RSNOs (7.2 +/- 1.1 nmol/l). Both N- and S-nitroso moieties appear to be associated with the albumin fraction. This is the first report on the constitutive presence of a high-molecular-weight N-nitroso compound in the human circulation, raising the question as to its origin and potential physiological role. Our findings may not only have important implications for the transport of NO in vivo, but also for cardiovascular disease diagnostics and the risk assessment of nitrosamine-related carcinogenesis in man.

Adult↗
PubMed1987

Evaluation of the nitrosamine hypothesis of gastric carcinogenesis in man.

Patients who had undergone a Billroth II gastrectomy (PG) or had pernicious anaemia (PA) and healthy matched control subjects (MC) participated in 24-h studies in which bacteria, nitrite and N-nitroso compounds (NOC) were measured in gastric juice and N-nitrosoproline (NPRO) in urine. Consistent with the nitrosamine hypothesis, intragastric levels of bacteria and nitrite were positively related to intragastric pH, but, contrary to the hypothesis, NOC in gastric juice and NPRO in urine were negatively related to intragastric pH.

Anemia, Pernicious↗
PubMed1996

Bacterial overgrowth during treatment with omeprazole compared with cimetidine: a prospective randomised double blind study.

BACKGROUND: Gastric and duodenal bacterial overgrowth frequently occurs in conditions where diminished acid secretion is present. Omeprazole inhibits acid secretion more effectively than cimetidine and might therefore more frequently cause bacterial overgrowth. AIM: This controlled prospective study compared the incidence of gastric and duodenal bacterial overgrowth in patients treated with omeprazole or cimetidine. METHODS: 47 outpatients with peptic disease were randomly assigned to a four week treatment regimen with omeprazole 20 mg or cimetidine 800 mg daily. Gastric and duodenal juice were obtained during upper gastrointestinal endoscopy and plated for anaerobic and aerobic organisms. RESULTS: Bacterial overgrowth (> or = 10(5) cfu/ml) was present in 53% of the patients receiving omeprazole and in 17% receiving cimetidine (p < 0.05). The mean (SEM) number of gastric and duodenal bacterial counts was 6.0 (0.2) and 5.0 (0.2) respectively in the omeprazole group and 4.0 (0.2) and 4.0 (0.1) in the cimetidine group (p < 0.001 and < 0.01; respectively). Faecal type bacteria were found in 30% of the patients with bacterial overgrowth. Basal gastric pH was higher in patients treated with omeprazole compared with cimetidine (4.2 (0.5) versus 2.0 (0.2); p < 0.001) and in patients with bacterial overgrowth compared with those without bacterial overgrowth (5.1 (0.6) versus 2.0 (0.1); p < 0.0001). The nitrate, nitrite, and nitrosamine values in gastric juice did not increase after treatment with either cimetidine or omeprazole. Serum concentrations of vitamin B12, beta carotene, and albumin were similar before and after treatment with both drugs. CONCLUSIONS: These results show that the incidence of gastric and duodenal bacterial overgrowth is considerably higher in patients treated with omeprazole compared with cimetidine. This can be explained by more pronounced inhibition of gastric acid secretion. No patient developed signs of malabsorption or an increase of N-nitroso compounds. The clinical significance of these findings needs to be assessed in studies with long-term treatment with omeprazole, in particular in patients belonging to high risk groups such as HIV infected and intensive care units patients.

Adult↗
PubMedDate not supplied

[Production of mutants with an increased alpha-amylase synthesis].

A mutant characterized by elevated biosynthesis of alpha-amylase was obtained as a result of a three-stage induced selection using nitroso compounds. Changes of mutagens in the course of selection stages and the establishment of their effective doses causing the maximum accumulation of mutations yielded the mutant which produced 2.5 times more alpha-amylase than the parent strain of Aspergillus oryzae 762. The induced variability of the mutant can be registered on a solid growth medium and provides the high activity of alpha-amylase.

Amylases↗
PubMed1992

Involvement of alkylating agents in schistosome-associated bladder cancer: the possible basic mechanisms of induction.

Carcinoma of the urinary bladder is a common malignancy in many tropical and subtropical countries. There is a well documented sequela of chronic urinary schistosomal infection and bladder cancer associated with schistosomiasis is a major cause of morbidity and mortality in the endemic areas. Experimental bladder cancer can be induced in schistosome-infected animals. Multiple factors have been suggested as causative agents in schistosome-associated bladder carcinogenesis and the N-nitroso compounds appear to be of particular importance. These agents have long been suspected to play a major role in the aetiology of a variety of human cancers. A model for the induction of bladder cancer associated with schistosomiasis is proposed which takes into account the interrelationships between different factors resulting from the infection, especially the role of alkylating agents that can contribute to the induction of this neoplasm.

Alkylating Agents↗