SEARCH · Search PubMed

Results for “NITROSAMINES”

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.

SourceResearch connectionFrom yearThrough year

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

At least 469 records · Page 26Linked to original sources

PubMed2002

Helicobacter pylori does not mediate the formation of carcinogenic N-nitrosamines.

BACKGROUND: Both N-nitroso compounds and colonization with Helicobacter pylori represent known risk-factors for the development of gastric cancer. Endogenous formation of N-nitroso compounds is thought to occur predominantly in acidic environments such as the stomach. At neutral pH, bacteria can catalyze the formation of N-nitroso compounds. Based on experiments with a noncarcinogenic N-nitroso compound as end product, and using only a single H. pylori strain, it was recently reported that H. pylori only displays a low nitrosation capacity. As H. pylori is a highly diverse bacterial species, it is reasonable to question the generality of this finding. In this study, several genetically distinct H. pylori strains are tested for their capacity to form carcinogenic N-nitrosamines. MATERIALS AND METHODS: Bacteria were grown in the presence of 0-1000 microM morpholine and nitrite (in a 1 : 1 molar ratio), at pH 7, 5 and 3. RESULTS: Incubation of Neisseria cinerea (positive control) with 500 microM morpholine and 500 microM nitrite, resulted in a significant increase in formation of N-nitrosomorpholine, but there was no significant induction of N-nitrosomorpholine formation by any of the H. pylori strains, at any of the three pH conditions. CONCLUSION: H. pylori does not induce formation of the carcinogenic N-nitrosomorpholine in vitro. The previously reported weak nitrosation capacity of H. pylori is not sufficient to nitrosate the more difficulty nitrosatable morpholine. This probably also holds true for other secondary amines. These results imply that the increased incidence of gastric cancer formation that is associated with gastric colonization by H. pylori is unlikely to result from the direct induced formation of carcinogenic nitrosamines by H. pylori. However, this has to be further confirmed in in vivo studies.

Antigens, Bacterial↗

PubMed1983

Metabolism of tobacco-specific N-nitrosamines by cultured human tissues.

N'-Nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are present in cigarette smoke and snuff and are carcinogens in laboratory animals. In tobacco smokers, the buccal mucosa, trachea, esophagus, bronchi, and peripheral lung are exposed to smoke containing significant amounts of these N-nitrosamines. The results of the present study demonstrate that explants of these tissues as well as of the urinary bladder have the capacity to metabolize NNN and NNK by alpha-carbon hydroxylation. This metabolic pathway yields alkyldiazohydroxides, which are reactive and DNA-damaging electrophiles. The extent of alpha-carbon hydroxylation of NNN and NNK in human tissues was only 1/10th to 1/100th of that in animal tissues. Although the levels of alpha-carbon hydroxylation of NNN among different tissues of the same individual were similar, a 10-fold variation among individuals was observed. Reduction of the NNK carbonyl group was a major metabolic pathway observed with all human explants and may occur in the surface epithelia of the respiratory tract of smokers. These results provide further evidence that tobacco-specific N-nitrosamines could play a role in cancers related to the smoking and chewing of tobacco.

Biotransformation↗

PubMed1992

A tobacco-specific N-nitrosamine or cigarette smoke condensate causes neoplastic transformation of xenotransplanted human bronchial epithelial cells.

Using a xenotransplantation system in which immortalized nontumorigenic human bronchial epithelial cells (BEAS-2B cells) are grown in deepithelialized rat tracheas that are subcutaneously transplanted into athymic nude mice, we exposed BEAS-2B cells either to cigarette smoke condensate or to the tobacco-specific N-nitrosamine 4-(methylnitrosamine)-1-(3-pyridyl)-1- butanone. After 6 mo the carcinogen-exposed BEAS-2B cells were neoplastically transformed to invasive adenocarcinomas. Cell lines obtained from xenografts exposed in vivo to chemicals exhibited several features typical of malignant lung cancer cells, such as increased in vivo invasiveness that correlated well with enhanced type IV collagenolytic activity, resistance to serum-induced growth inhibition, and increased expression of transforming growth factor alpha and its cellular-membrane receptor. Invasiveness, similar to that seen after exposure to phorbol esters, was also detected after in vitro exposure of BEAS-2B cells to cigarette smoke condensate. Collectively, these data indicate that cigarette smoke condensate and N-nitrosamine 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone induce in vivo phenotypic changes in BEAS-2B cells similar to the progressive changes that occur during human lung carcinogenesis.

Animals↗

PubMed1983

Potassium nitrate and nitrosamine formation.

The influence of potassium nitrate on the formation of nitrosamines in salami was studied. Samples of salami were prepared, with and without the addition of potassium nitrate. Under the conditions of the experiment, potassium nitrate did not represent a source of either nitrite or nitrosamines. Independently of the presence of potassium nitrate in the sample formulation, the growth of bacterial flora reached a maximum in the first 20 days of the ripening process.

Bacteria↗

PubMed2003

Migration of N-nitrosamines, N-nitrosatable substances and 2-mercaptobenzthiazol from baby bottle teats and soothers: a Dutch retail survey.

In 2001, a retail market survey of 19 samples of teats and soothers was performed in the Netherlands. The migration of 2-mercaptobenzthiazol (MBT), N-nitrosamines and nitrosatable substances was measured. A screening was also performed for other potential migrants. Of the soothers, shield size and yield strength were determined. Most of the teats and soothers on the Dutch market were made of silicone rubber, although a few were made of natural rubber. The migration of N-nitrosamines and nitrosatable substances was far below the migration limit of 0.01 and 0.1 mg kg(-1) teat, respectively, with the exception of one natural rubber soother. For this soother, the migration of nitrosatable substances was 0.23 mg kg(-1) and measures were therefore taken against the supplier. MBT was detected in only one natural rubber sample, migration being well below the limit of 0.3 mg/teat. The extractable substances in the silicone teats and soothers are siloxanes. From the two natural rubber products, substances were extracted that were not on the positive list of the Dutch Packaging and Food-Utensils Regulation. Most of these substances are allowed in other countries, or authorized for plastic food contact materials. The size of the shields of all soothers and yield strengths were in compliance with the Regulation.

Benzothiazoles↗

PubMedDate not supplied

Volatile nitrosamines in foods on the Swedish market and estimation of their daily intake.

Foods on the Swedish market in 1980-1986 were analysed for volatile N-nitrosamines using gas chromatography-thermal energy analysis. Detectable levels were found in 474 of the 764 samples analysed. The average daily intake of volatile N-nitrosamines was estimated to be 0.29 microgram per person. Over 93% of the intake comes from meat and malt products.

Animals↗

PubMedDate not supplied

Volatile N-nitrosamines in Polish malt and beer.

A survey of Polish malt and beer for volatile N-nitrosamines has been conducted. N-Nitrosodimethylamine was found in malt at levels ranging from 0.2 to 3.6 micrograms/kg (average 1.5 micrograms/kg) and in beer at levels up to 0.3 microgram/kg (average 0.2 micrograms/kg). The use of indirect malt dryers is credited with the low levels of N-nitrosamines found.

Beer↗

PubMed1998

Application of liquid chromatography-atmospheric pressure chemical ionization mass spectrometry and tandem mass spectrometry to the determination of volatile nitrosamines in dry sausages.

A high-performance liquid chromatographic-atmospheric pressure chemical ionization mass spectrometric method was developed for the determination of volatile nitrosamines in dry sausages. Tandem mass spectrometry was applied for the detection of N-nitrosopyrrolidine, N-nitrosodiethylamine and N-nitrosopiperidine. N-nitrosomethylamine was detected by using the selected ion monitoring mode. The occurrence of the four different nitrosamines was monitored in 27 dry sausage samples and a correlation was observed between N-nitrosopyrrolidine and biogenic amines. Nitroso compounds are thus not only formed in heated conditions but formation can also occur during ripening of dry sausages by reaction between residual nitrite and amines formed during the fermentation process.

Animals↗

PubMed1979

Measurement of the aquatic toxicity of volatile nitrosamines.

The acute toxicity of N-nitrosodimethylamine (DMN) and N-nitrosodiethylamine (DEN) was determined for three groups of aquatic organisms: algae, invertebrates, and fish. Toxicity of DMN and DEN to algae was assessed as a repression in the growth rate of either Selenastrum capricornutum or Anabaena flos-aquae in static bioassay tests. DMN and DEN concentrations of 1-10 ppm depressed algal growth in all cases. Invertebrate toxicity was determined in 96-h static bioassay tests with Dugesia dorotocephala and Gammarus limnaeus. The data indicated that these organisms are not highly susceptible to nitrosamine toxicity. The 96-h LC50s for D. dorotocephala were 1365 and 1490 ppm for DMN and DEN, respectively. Similar studies with G. limnaeus indicated LC50s of 330 and 500 ppm for DMN and DEN, respectively. Fish toxicity was also determined in 96-h statis bioassays with the fathead minnow (Pimephales promelas). Acute toxicities were calculated as LC50s of 940 and 775 ppm for DMN and DEN, respectively. Algae were calculated as LC50s of 940 and 775 ppm for DMN and DEN, respectively. Algae were quite sensitive to relative low levels of volatile nitrosamines, but higher organisms (invertebrates and fish) were relatively insensitive.

Animals↗

PubMed2000

Exposure to nitrosamines, carbon black, asbestos, and talc and mortality from stomach, lung, and laryngeal cancer in a cohort of rubber workers.

There is sufficient evidence for an excess occurrence of stomach and lung cancer among rubber workers. However, evidence for causal associations with specific exposures is still limited. A cohort of 8,933 male German rubber workers was followed for mortality from January 1, 1981 through December 31, 1991. Work histories were reconstructed using routinely documented cost center codes. For each cost center code, calendar time-and plant-specific levels of exposure to nitrosamines, asbestos, talc (low, medium (m), and high (h)), and carbon black (two levels) were estimated by industrial hygienists. Rate ratios (RR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards models, with the lowest exposure level used as the reference category. Exposure was lagged 10 years to account for latency. Exposure-response relations between exposure to asbestos and lung cancer mortality (RRm = 1.3, 95% CI: 0.9, 1.9; RRh = 2.0, 95% CI: 0.9, 4.1) and between exposure to dust (talc and asbestos combined) and stomach cancer mortality (RRm = 1.8, 95% CI: 0.9, 3.8; RRh = 2.7, 95% CI: 1.0, 7.1) were observed. Exposure to nitrosamines was not associated with mortality from stomach or lung cancer. These results suggest that the increased mortality from lung and stomach cancer among rubber workers is associated with exposure to asbestos and dust, respectively.

Aged↗

PubMed1989

Cell specificity for the pulmonary metabolism of tobacco-specific nitrosamines in the Fischer rat.

The activity and distribution of the metabolic pathways of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), its major metabolite 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and the structurally related nitrosamine, N'-nitrosonornicotine (NNN) were examined in pulmonary cells from F344 rats in order to investigate the mechanisms by which NNK and NNAL, but not NNN, cause lung tumors. The tritium labeled nitrosamines were incubated with Clara cells, alveolar macrophages, alveolar type II cells, or small cells and metabolites were analyzed by HPLC. O6-Methyl-guanine (O6MG) formation was also quantified in the cells incubated with NNK. Clara cells metabolized all compounds more extensively than the other cell types. Total alpha-hydroxylation, carbonyl reduction to NNAL, and pyridine N-oxidation in cells incubated with NNK, as well as concentrations of O6MG in DNA were higher in Clara cells than in other cell types. Carbonyl reduction of NNK predominated over the other metabolic pathways in all cell types. The high activity for alpha-hydroxylation of NNK in Clara cells is consistent with previous studies which proposed that the cell specificity for O6MG formation and the accumulation of this adduct during low-dose exposure to NNK may stem from the presence of a high affinity pathway in Clara cells for NNK activation. Metabolism of NNAL by alpha-hydroxylation, and by reconversion to NNK followed by alpha-hydroxylation were observed. Total alpha-hydroxylation of NNAL was less extensive than alpha-hydroxylation of NNK. NNN was metabolized by both the 2'- and 5'-alpha-hydroxylation pathways. 2'-Hydroxylation of NNN produces the same DNA pyridyloxobutylating agent as does methyl hydroxylation of NNK. However, NNN is not a methylating agent and does not induce lung tumors in rats. Metabolism of NNN by 2'-hydroxylation was, depending on cell type, 41-85% as extensive as total alpha-hydroxylation of NNK, indicating that the rates of formation of the DNA pyridyloxobutylating agent were similar from NNN and NNK. The results of this study demonstrate that Clara cells have a high capacity to metabolically activate NNK, NNAL and NNN and provide further support for the hypothesis that DNA methylation of pulmonary cells is important in NNK carcinogenesis.

Alkylation↗

PubMed1990

Investigations on the origin of tobacco-specific nitrosamines in mainstream smoke of cigarettes.

The origin of tobacco-specific nitrosamines (TSNA) in mainstream smoke and the possible contribution of synthesis during the smoking procedure was investigated. Addition of the nitrosamine precursors nitrate and nicotine to the tobacco prior to smoking did not change the mainstream smoke concentrations of N'-nitrosonornicotine (NNN) and 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), whereas the mainstream smoke concentration of N'-nitrosoanabasine (NAB) and N'-nitrosoanatabine (NAT) increased after spiking the cigarettes with nitrate. Data for TSNA in tobacco and in mainstream smoke and for nitrate in tobacco of commercial cigarettes of the West German market, taken from previous investigations, were used to calculate the mainstream smoke/tobacco ratios for NNN and NNK. These ratios were corrected for ventilation and cigarette length. It is shown that the ratios are constant and neither depend on the nicotine level nor on the nitrate level of the tobacco except for NNK in the nitrate rich dark tobacco type cigarettes. For nonfilter cigarettes the transfer rates of NNN and NNK which had been corrected for ventilation and cigarette length amounted to 23 or 34% respectively. For filter cigarettes a transfer rate of 13% for NNN and 23% for NNK was calculated. Furthermore it is shown that the mainstream smoke/tobacco ratios for NNN and NNK are constant over the whole length of the cigarettes except for NNK in dark tobacco type cigarettes. The results of this investigation indicate that pyrosynthesis of NNN does not occur and that it is very unlikely for NNK at least for lower nitrate levels. Thus with few exceptions the TSNA burden of smokers is predominantly influenced by the amount of preformed NNN and NNK in tobacco.

Carcinogens↗

PubMed1991

Role of ras protooncogene activation in the formation of spontaneous and nitrosamine-induced lung tumors in the resistant C3H mouse.

The role of ras activation in the formation of spontaneous and chemically induced tumors was evaluated in the C3H mouse, a strain that has a low incidence of spontaneous lung tumors. Lung tumors were induced in C3H mice by treatment with 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 50 mg/kg, or nitrosodimethylamine (NDMA), 3 mg/kg for 7 weeks (3 times/week, i.p.). Eleven tumors from each treatment group were evaluated for activated ras genes by direct sequencing and oligonucleotide hybridization to slot blots of amplified DNA from these tumors. An activated K-ras gene was detected in 100% of NDMA- and NNK-induced lung tumors, and the activating mutation detected in all samples was a GC to AT transition (GGT to GAT) in codon 12. In contrast, only 40% of the seven spontaneous lung tumors analyzed contained an activated K-ras gene and the mutations identified were not localized to either a specific base or codon. Both NNK and NDMA can be activated via alpha-hydroxylation to methylating agents. The GC to AT mutation observed in codon 12 in the nitrosamine-induced tumors is consistent with the formation of an O6-methylguanine (O6MG) adduct. Similar concentrations (13-15 pmoles/mumol deoxyguanosine) of this promutagenic adduct were detected in lungs during treatment with either NNK or NDMA. Thus, both these nitrosamines appear to activate the K-ras gene in lung through a direct genotoxic mechanism involving the formation of the O6MG adduct. The frequency of K-ras activation was similar in chemically induced lung tumors from the sensitive A/J strain and the C3H mouse, indicating that susceptibility for neoplasia in these stains is not related to the ability to activate this gene. Although tumors were induced in lung from 100% of C3H mice following chronic carcinogen exposure, both the size and the multiplicity was significantly less, while latency was longer than that observed in the A/J mouse. These differences could not be attributed to an altered propensity for DNA damage, but rather suggest that genetic loci which regulate clonal expansion and growth of initiated cells play a major role in the susceptibility of pulmonary neoplasia.

Animals↗

PubMed1991

Selective cytotoxicity of N-nitrosamines to cultured rat esophageal epithelial cells.

The rat esophageal carcinogen N-nitrosomethylbenzylamine was shown to be highly toxic to rat esophageal epithelial (REE) cells in short-term primary culture. A significant level of cell killing could be observed at 10(-6) M. Several other esophageal carcinogens were also cytotoxic in a dose-dependent manner. Nitrosamines that do not produce esophageal tumors in the rat were generally unable to kill the esophageal cells. The results demonstrate that REE cells retain their metabolic capacity to activate specific nitrosamines to toxic metabolites. The culture system will be useful for mechanistic studies on the tissue specificity of these carcinogens, as well as to search for environmental agents that kill esophageal cells that may be involved in the causation of esophageal cancer.

Animals↗

PubMed1991

Endogenous formation of N-nitrosamines from piperazine and their urinary excretion following antihelmintic treatment with piperazine citrate.

Antihelmintic treatment with piperazine (1,4-diazacyclohexane) for microfilarie parasitism results in the endogenous formation of piperazine-derived N-nitrosamines. The urinary excretion of these N-nitrosamines was determined by biochemical monitoring of 14 patients receiving 2 g piperazine citrate. The urinary excretion (mean +/- SD) of N-mononitrosopiperazine (MNPz) was 27.0 +/- 26.7 micrograms/day (range 0.6-96.0 micrograms/day). Trace levels of 0.73 +/- 0.92 micrograms/day N,N'-dinitrosopiperazine (DNPz) (range ND-2.8 micrograms/day) were also found in 7 of 14 urine samples. N-Nitroso-3-hydroxypyrrolidine (NHPYR), a metabolite of both MNPz and DNPz, was detected in 11 of 14 urine samples at a mean concentration of 1.74 +/- 1.72 micrograms/day (range ND-5.7 micrograms/day) and traces of N-nitrosodiethanolamine in two samples at levels of 0.3 and less than 0.1 micrograms/day. The results show that biochemical monitoring of urinary NHPYR may be a good indicator of endogenous MNPz formation. While DNPz was also detected in urine, conclusive validation for its endogenous formation could not be provided because no evidence was found for the presence of its major metabolite, N-nitroso-(2-hydroxyethyl)glycine in urine.

Adult↗

PubMed1992

Secondary amine precursors to nitrosamines in human saliva, gastric juice, blood, urine and faeces.

It has been suggested that the endogenous nitrosation of aliphatic, cyclic and heterocyclic secondary amines in the urinary bladder of patients with chronic urinary bacterial infections and in the human stomach may provide an important additional source of exposure to carcinogenic volatile N-nitrosamines. The most commonly occurring nitrosatable secondary amines found in human saliva, gastric juice, blood, urine and faeces are dimethylamine (DMA), pyrrolidine (PYR) and piperidine (PIP). All of 40 analysed samples of gastric juice contained 0.87 +/- 0.89 (SEM) microgram/ml DMA, 39 contained 1.35 +/- 2.53 microgram/ml PIP, 36 contained 0.18 +/- 0.15 microgram/ml PYR and 14 contained 0.05 +/- 0.11 microgram/ml diethylamine. Nitrate (14.0 +/- 15.7 microgram/ml) was present in all samples and 11 of 40 samples contained 0.43 +/- 1.38 microgram/ml nitrite. Only one gastric juice sample with pH less than 4.5 contained nitrite (0.1 microgram/ml). In paraplegics, patients with bladder augmentations and two control groups without bacterial infections of the urinary bladder, a mean daily excretion of 40.5-49.7 mg/day DMA, 19.4-23.8 mg/day PYR and 26.1-31.7 mg/day PIP was found. In both patient groups suffering from chronic bacterial infection of the urinary bladder, the corresponding volatile N-nitrosamines were formed by endogenous nitrosation and excreted in urine.

Bacteria↗

PubMed1993

Metabolism of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in the patas monkey: pharmacokinetics and characterization of glucuronide metabolites.

The metabolism of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was examined in the patas monkey, in order to provide further information about NNK metabolic pathways in primates. Female patas monkeys were given i.v. injections of [5-3H]NNK, and metabolites in serum and urine were analyzed by HPLC. Metabolism by alpha-hydroxylation of NNK was rapid and extensive, and the products of this pathway, 4-hydroxy-4-(3-pyridyl)butyric acid and 4-oxo-4-(3-pyridyl) butyric acid, accounted for a relatively large proportion of serum and urinary metabolites at all time points. This is significant because the formation of these products is associated with modification of DNA by NNK. The other major metabolic pathway was carbonyl reduction to 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), which detected both unconjugated and diastereomeric O-glucuronides. One of these glucuronides had been previously identified in rat urine, but the other diastereomer, which was the more prevalent of the two in serum and urine, had not been observed in studies of NNK metabolism in rodents. It was characterized by its spectral properties, by enzymatic hydrolysis to NNAL, and by derivatization of the released NNAL enantiomer with (R)-(+)-alpha-methylbenzylisocyanate. The two NNAL glucuronides accounted for 15-20% of the urinary metabolites in monkeys given 0.1 micrograms/kg NNK, which is similar to a smoker's dose, suggesting their use as dosimeters of NNK exposure in humans. Pharmacokinetic parameters were consistent with those observed in previous studies of nitrosamines, and varied predictably with body weight of five species. The results of this study have provided new insights relevant to assessing human metabolism of NNK.

Animals↗

PubMed1981

The relationship between the carcinogenicity and mutagenicity of nitrosamines in a hepatocyte-mediated mutagenicity assay.

A quantitative relationship was established for 26 nitrosamines between their carcinogenic effectiveness in experimental animals and their mutagenic activity in a mammalian cell-mediated assay. Mutagenesis was measured in Chinese hamster V79 cells co-cultivated with primary rat hepatocytes, which are capable of activating nitrosamines. Resistance to ouabain and to 6-thioguanine served as the genetic markers.

Animals↗