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At least 343 records · Page 19Linked to original sources
PubMed1987

N-nitrosamine formation by macrophages.

Nitrate biosynthesis is a known mammalian process, and macrophages from mice treated with Escherichia coli lipopolysaccharide (LPS) have been shown to be capable of nitrate synthesis. Cell culture studies showed that macrophages produce nitrite as well as nitrate. We report here N-nitrosamine formation by stimulated macrophages. Experiments were carried out with the macrophage cell lines, J774.1, WEHI-3 and RAW 264. Macrophages were cultured in Dulbecco's modified Eagle's medium (pH 7.5) supplemented with calf serum (10%). The concentration of nitrate in the supernatant was measured. N-nitrosamines were extracted with dichloromethane and the extracts were analysed by gas chromatography-thermal energy analysis. When J774.1 (1.5 X 10(6) cells/ml) were incubated with LPS (10 micrograms/ml) and morpholine (15 mM) for 72 h at 37 degrees C, N-nitrosomorpholine (NMOR) was produced (0.8 microM). The amount of nitrite produced was 50 microM. RAW 264 and WEHI-3 also produced NMOR; LPS was required for nitrite and NMOR formation. gamma-Interferon (IFN) promoted both NMOR (2.5 microM) and nitrite (70 microM) formation. Nitrite (150 microM) incubated with morpholine and the medium did not form NMOR. Kinetics of LPS-induced nitrite and NMOR formation in J774.1 showed that the rate of NMOR formation was highest in the middle incubation period (24-36 h), although the nitrite concentration was highest in the latter incubation period (48-60 h). Our results showed that macrophages may be capable of nitrosamine formation under physiological conditions that do not normally permit this reaction.

Animals↗
PubMed1987

Nitrosamine measurements in ambient air of an industrial area in Austria.

The area of Linz (Oberösterreich) is the most heavily polluted region in Austria, due to its chemical and steel industry. In 1981, a survey of volatile nitrosamines in ambient air performed by a local laboratory revealed levels of up to 5.45 micrograms/m3. This instigated the setting up of a systematic nitrosamine monitoring programme from February 1983 to May 1984, during which the validity of the analytical procedures was determined. A total of 363 air samples was collected over 200 days at 16 different locations in and around Linz. About 6% of the samples showed low nitrosamine contamination, with levels between 0.01 and 0.04 microgram/m3 of N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), and N-nitrosomorpholine (NMOR). The lower limit of detection was 0.005 microgram/m3. It was not possible to confirm these low concentrations by high-resolution mass spectrometry. In some samples, thermal energy analyser-responsive material was observed, which may be due to the occurrence of C-nitro compounds.

Air Pollution↗
PubMed1985

Association of nitrosamine-derived radioactivity with nuclear and mitochondrial DNA in mice.

In order to better understand the carcinogenic process, a comparative study was undertaken of the association of nitrosamine-derived radioactivity with nuclear and mitochondrial DNA isolated from tumor-susceptible and non-tumor-susceptible tissues of two strains of mice with different susceptibilities to tumor induction by dimethylnitrosamine (DMN) or diethylnitrosamine (DEN). A single dose of either [14C]-DMN or [14C]DEN was administered by intragastric intubation to young adult male RFM or BALB/c mice. The DNA isolated from the mitochondrial fraction of tumor-susceptible tissues bound several times (10 to 90) more nitrosamine than the nuclear DNA. These results suggest that mitochondrial DNA may be a target in the carcinogenic process induced by nitrosamine compounds.

Animals↗
PubMed1979

Volatile N-nitrosamines in the urine of normal donors and of bladder cancer patients.

Volatile N-nitrosamines were detected in the urine of male volunteers with gas-liquid and high-pressure liquid chromatography interfaced to the thermal energy analyzer. Of 50 samples from normal males, 10 contained nitrosodimethylamine (0.02 to 0.10 micrograms/liter), 6 contained nitrosodiethylamine (0.02 to 3.10), 9 contained nitrosomorpholine (0.006 to 0.67), and none contained nitrosodibutylamine. Of 4 samples from bladder cancer patients, 2 contained nitrosodibutylamine (0.35 and 0.66). Cigarette smoking did not appear to be related to the pattern or amount of urinary volatile N-nitrosamines. The possibility that the N-nitrosamines arise from the diet or from endogenous production is considered.

Adult↗
PubMed1978

Analysis for volatile nitrosamines in salt-preserved foodstuffs traditionally consumed by southern Chinese.

Six types of salted fish and 10 other sorts of salted food products traditionally consumed by southern Chinese were analysed by GC-MS for the presence of volatile nitrosamines. The detection limit in the original raw food was 1 microg/kg for each nitrosamine. Only NDMA, in the range of 1-35 microg/kg, could be detected, in four of the six types of salted fish samples examined; and no nitrosamines were found in the other salted food products.

Animals↗
PubMed1982

Nitrosamines and their precursors in some Kazakh foodstuffs.

Numerous samples of various foods, such as salt-dried and smoke-dried meats, fermented sausages, sour-milk products, fermented mare's and camel's milk, raw vegetables, rice, rock and table salts, local bread and daily food rations were analysed by GC-TEA and HPLC-TEA for the presence of volatile nitrosamines. Apart from the observation of NDMA (up to 0.7 microgram/kg) in three samples of Kazakh cheeses, the volatile nitrosamines were detected only in some meat and meat products. Salted air-dried meat contained NDMA in amounts up to 54 micrograms/kg. NPYR (12 micrograms/kg) was found in one sample of nitrite-cured sausage. The highest content of NPIP (7 micrograms/kg) was detected in fermented, home-made sausage. It is clear that the only significant contribution of these dialkyl and heterocyclic nitrosamines to the diet is from stored, salt-dried meat and nitrite-cured meat products. Analyses of nitrate and nitrite in various local products are reported. The validity of our assumption that the high incidence of oesophageal cancer can be lowered by realistic improvements in the processing and storage of meat and meat products requires further evaluation.

Food Analysis↗
PubMed1983

Drug interactions. III. Formation of nitrosamines from therapeutic drugs. Formation, mutagenic properties and safety assessment of propranolol hydrochloride with respect to the intragastric formation of N-nitrosopropranolol under conditions found in patients.

In the preceding report, the kinetics of formation of N-nitrosopropranolol (NNP) from propranolol and inorganic nitrite were determined in solutions of hydrochloric acid over the range of pH similar to that found in the human stomach. In this communication, NNP formation was examined in human gastric juice and in the presence of organic nitrate ester vasodilator drugs. In comparison to HCl solutions, equivalent concentrations of propranolol and nitrite produced similar amounts of NNP in gastric juice; however, the yield increased as the pH was lowered and the kinetics of nitrosamine formation were different. Endogenous nitrite concentrations in 22 samples of human gastric juice were below the minimum concentration (10(-5) M) required for production of detectable levels of NNP. Maximal therapeutic dosages of propranolol (10(-2) M) incubated with isosorbide dinitrate (3,4-6.8 X 10(-3) M) or nitroglycerin (8.6 X 10(-4) M) also failed to produce NNP. However, NNP formed adventitiously during the concentration of aqueous and methylene chloride solutions that contained propranolol and organic nitrates, underscoring the importance of avoiding artifactual formation of nitrosamines. Furthermore, synthetic NNP was not mutagenic in either the Ames tester strains (TA92, TA98, TA100, TA1535, TA1537 and TA1538) or the hepatocyte-mediated mammalian cell mutagenesis assay. We conclude that NNP is unlikely to form in the stomach under conditions normally present in patients. Moreover, even if NNP formed under exceptional circumstances, this compound is unlikely to be a carcinogen. With respect to the potential formation of nitrosamines during drug dissolution in the stomach, long-term therapy with propranolol hydrochloride appears to be safe.

Biotransformation↗
PubMed1984

alpha-Hydroxylation of nitrogen-15 labelled N-nitrosamines by isolated hepatocytes.

The principal pathway of nitrosamine metabolism has long been considered to be alpha-hydroxylation. For N-nitrosodialkylamines, this hypothesis requires that a molecule of molecular nitrogen be released for every molecule of nitrosamine that is alpha-hydroxylated. Thus, the quantitative determination of nitrogen formation should provide a measure of the importance of this pathway. This method was applied earlier to the doubly-labelled nitrogen-15 compounds, N-nitrosodimethylamine (NDMA), N-nitrosomethylphenylamine (NMPhA) and N-methyl-N-nitrosourea (MNU), using both a 9 000 X g supernatant fraction of liver and the intact animal as metabolic systems. The in-vitro results were quite different from those obtained in vivo. The majority of the NDMA (67%) and the MNU (88%) were converted to nitrogen in vivo, while NMPhA gave considerably less nitrogen (52%). These results differed by a factor of approximately two from those obtained in vitro (NDMA, 33%; NMPhA, 18.8% and MNU, 96%). Since such differences may be a result of the loss of cellular architecture, we have extended the work to include isolated hepatocytes. It had been shown previously that isolated hepatocytes constitute a practical alternative to in-vivo systems, even though the correlation with in-vivo metabolism appears to depend on the substrate analysed. The values obtained using this system (NDMA, 47%; NMPhA, 23%; and MNU 105%) reconfirm that metabolism may be substrate dependent. As in our previous studies, no mixed nitrogen (15N14N) or labelled nitrogen oxides were found. The data are all consistent with the hypothesis that at least one demethylase for each of the nitrosamine substrates is associated with a cell membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Metabolic inactivation of N-nitrosamines by cytochrome P-450 in vitro and in vivo.

Nitrite was formed on incubation of N-nitrosamines with both microsomal systems and a reconstituted system consisting of cytochrome P-450 and NADPH P-450 reductase from pig liver. Nitrite was not obtained when the nitrosamines were incubated with NADPH P-450 reductase alone or when molecular oxygen or NADPH was omitted. Various inhibitors of the microsomal monooxygenase decreased nitrite generation. Furthermore, nitrite and a substantially higher amount of nitrate could be found in the urine of rats given N-nitrosodiphenylamine. Diphenylamine was also detected. From in-vitro studies, it is concluded that denitrosation of N-nitrosamines is a cytochrome P-450-dependent process, which also occurs in vivo.

Animals↗
PubMed1984

A study of betel quid carcinogenesis. II. Formation of N-nitrosamines during betel quid chewing.

In model studies, nitrosation of the major areca alkaloid, arecoline, leads to the formation of N-nitrosoguvacoline, 3-(methylnitrosamino)propionitrile (MNPN), 3-(methylnitrosamino)propionaldehyde and two unknown N-nitrosamines. MNPN is a strong carcinogen in Fischer 344 rats. After subcutaneous injection of 1.1 mmol MNPN in 60 doses, all 15 male and 15 female rats developed tumours within 24 weeks; multiple tumours occurred in 26 of the rats. Eighty-seven percent of the animals had tumours of the oesophagus, 70% had nasal cavity tumours, 37% had tumours of the tongue, 7% tumours of the pharynx and 7% tumors of the forestomach. At the dose used, male and female rats showed no significant difference in tumour incidence or site of tumours. The formation of MNPN during betel quid chewing, although likely, has not yet been proven, while the areca-derived N-nitrosamine, N-nitrosoguvacoline (NG), has been found in the saliva of betel quid chewers at levels of 2.2-348 micrograms/L. N-Nitrosoguvacoline levels were higher in the saliva of chewers who used betel quid together with tobacco. The saliva of these chewers also contained tobacco-specific N-nitrosamines.

Animals↗
PubMedDate not supplied

[N-nitrosamine content in sausage products manufactured using protein preparations].

The content of carcinogenous N-nitrosamines was measured in protein preparations and sausages manufactured with the use of these preparations. Isolates from sunflower and soybean proteins and casein as well as sausages manufactured with the use of the indicated proteins did not differ from control samples as regards the content of nitrosamines. However, up to 6 micrograms/kg N-nitrosodimethylamine was detected in fish protein isolates. The content of nitrosamines in sausages manufactured with the use of fish protein appeared to be higher than in control.

Animals↗
PubMed1983

Survey of baby bottle rubber nipples for volatile N-nitrosamines.

A local market survey of 27 baby bottle rubber nipples for volatile N-nitrosamines was conducted. N-Nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosodibutylamine, and N-nitrosopiperidine were found at levels up to 387 ppb. All 4 nitrosamines migrated from the rubber nipples into water, milk, and infant formula when sterilized together in a manner typical of that used in the home. The source of the nitrosamines is the chemical accelerators and stabilizers added to raw rubber during the vulcanization process.

Animals↗
PubMed1978

The permeability of laboratory gloves to selected nitrosamines.

Samples of laboratory gloves of various composition and thicknesses were used as barriers between 0.136 M solutions of nitrosamines (dimethyl-, ethylmethyl-, diethyl-8 n-butylmethyl-, di-n-propyl-, di-iso-propyl- and di-sec-butyl- in dichloromethane, acetone, ethanol and double-distilled, deionized water) and water. The concentration of permeated nitrosamine was measured periodically. Nearly all gloves tested were permeable to the nitrosamine solutions. The results indicate that: (1) gloves should not be assumed to provide full protection, (2) gloves should be discarded immeidately following overt contamination and (3) gloves should not be reused.

Hand↗
PubMed1978

Electronic properties of the nitrosamine function.

The addition of a chiral alcohol, such as l-menthol or R-(-)-2-octanol, to an achiral nitrosamine causes a dissymmetric perturbation of the symmetrical chromophore and a Cotton effect is evident in the circular dichroism curve at the wavelength of ultraviolet absorption of the nitrosamine function. The intensity (ellipticity) of this induced circular dichroism is concentration dependent and appears to result from a weak 1:1 complex of nitrosamine and alcohol. The implications of these observations for structural studies are considered.

Chemical Phenomena↗
PubMed1983

N-nitrosamines in laboratory animal feed and bedding.

Volatile nitrosamine concentrations in laboratory animal feeds and bedding were determined by gas chromatography with a thermal energy analyzer. N-nitrosodimethylamine was detected in all samples of NIH-07 meal (range of 1.2 to 65.9 parts per billion) and 62% of NIH-07 pellet samples (0.6 to 35.2 parts per billion). It was also detected in 66% of closed formula meal (1.9 to 45.1 parts per billion) and 83% of closed formula pellets (0.2 to 21.3 parts per billion). Low concentrations were found in samples of hardwood chip and corncob bedding. Less frequently found in feed samples were N-nitrosodipropylamine, N-nitrosoethylmethylamine, and N-nitrosopyrrolidine. The latter was not detected in the closed formula diets. Traces of three nitrosamines (N-nitrosodimethylamine, N-nitrosodipropylamine, and N-nitrosomorpholine) were found in a single sample of AIN-76 mineral mix. These latter two nitrosamines and N-nitrosoethylmethylamine have not been reported previously in laboratory animal feeds.

Animal Feed↗
PubMedDate not supplied

[N-nitrosamines in beer and nonalcoholic beverages].

The content of carcinogenic N-nitrosamines was examined in beer, kvas, kvas wort, in dried pear and drink prepared from the dried fruit. An analysis was made with the use of the fluorescence technique. It was found that only some of the beer grades contain a negligible amount of N-nitrosamines. The remaining products showed no N-nitrosamines.

Beer↗
PubMed1982

Measurements by filter elution of DNA single- and double-strand breaks in rat hepatocytes: effects of nitrosamines and gamma-irradiation.

This work presents a filter elution method for measuring DNA single- and double-strand breaks in primary rat hepatocytes without radioactive labeling of DNA. We have studied the effects of a series of nitrosamines and of gamma-irradiation on DNA single- and double-strand break induction. The repair of DNA single-strand breaks in the hepatocytes was measured after treatment with 60Co, 1-methyl-1-nitrosourea, and N-nitrosodimethylamine. The hepatocytes were isolated by ethylene glycol-bis(beta-aminoethyl ether)-N,N'-tetra acetic acid-collagenase perfusion and had a mean viability of 91 +/- 4% (S.D.). The isolated cells were treated for varying lengths of time with nitrosamines in suspension culture in L-15 medium containing 10% fetal bovine serum. After treatment, the cells were chilled, loaded onto 2 micrometers polycarbonate filters, and lysed in a 2% sodium dodecyl sulfate-proteinase K solution, pH 9.6. The DNA was eluted from the filter at either native or denaturing pH with fractions collected every 3 hr. The quantity of DNA in each fraction was determined by measuring the fluorescent product formed between it and diaminobenzoic acid after ethanol-sodium acetate precipitation and trapping of the DNA on 0.2-micrometer polycarbonate filters. The results show that the carcinogens, N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosodipropylamine, N-nitrosodibutylamine, and 1-nitrosopiperidine all made dose- and time-related increases in the number of single-strand breaks in rat hepatocytes. N-Nitrosodiphenylamine produced small numbers of single-strand breaks. No double-strand breaks were formed by any of the nitrosamines. Single-strand breaks induced by N-nitrosodimethylamine were repaired very slowly relative to repair of either gamma-ray of 1-methyl-1-nitrosourea-induced single-strand breaks. This system has many advantages for studying carcinogen metabolism and DNA damage in hepatocytes, one of the major target cells for many carcinogens.-

Animals↗
PubMed1982

N-nitrosamines in grass silages.

During the fermentation of silages from nitrate-rich grass, the conditions are suitable for the formation of N-nitrosamines. Earlier investigations had shown that only low concentrations of volatile N-nitrosamines were formed. The first ten days of ensilage were investigated. The formation of nitrite was accompanied by the formation of volatile N-nitrosamines. NDMA and NDEA were detected in concentrations of up to about 2 micrograms/kg. After stabilisation of the silage, these concentrations dropped to about 0.6 microgram/kg. Preliminary results are presented concerning the presence of non-volatile N-nitroso compounds. The method of Walters et al. (1980) indicates that non-volatile N-nitroso compounds were present in amounts equivalent to 85 mg NPIP/kg sample.

Animal Feed↗