Search PubMed⌕ Search

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.

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

At least 1,477 records · Page 82Linked to original sources
PubMed1987

DNA methylation in rat tissues by a series of homologous aliphatic nitrosamines ranging from N-nitrosodimethylamine to N-nitrosomethyldodecylamine.

Aliphatic N-nitrosomethylalkylamines exhibit a remarkable organ specificity in rats, the principal targets for tumour induction being liver, oesophagus, urinary bladder and lung. We have determined the extent of DNA methylation in these tissues following a single oral dose (0.1 mmol/kg; 6 h survival) of each of 12 homologues, ranging from N-nitrosodimethylamine (C1) to N-nitrosomethyldodecylamine (C12). Methylpurines (7- and O6-methylguanine) were determined by cation exchange HPLC with fluorescence detection. Highest levels of hepatic DNA methylation were found with N-nitrosodimethylamine (C1) and N-nitrosomethylethylamine (C2), the most potent hepatocarcinogens in this series. Concentrations of methylpurines in liver DNA decreased with increasing chain length for C1-C5. Administration of the higher homologues (C6-C12) caused levels of DNA methylation which by themselves were considered too low to account for their hepatocarcinogenicity. In rat oesophagus, DNA methylation closely paralleled carcinogenicity, the butyl and pentyl derivatives (C4, C5) being most effective. In rat lung, the extent of DNA methylation was generally lower and there was no apparent correlation with carcinogenicity. Methylation of kidney DNA also decreased with increasing chain length and was only detectable for C1-C5. In urinary bladder DNA, methylpurines were below or close to the limit of detection. It is concluded that the initiation of malignant transformation by DNA methylation alone (through hydroxylation at the methylene alpha-carbon) could be operative for C1 in kidney and lung, for C1 and C2 in liver, and C3-C5 in oesophagus. For the higher homologues, the extent of DNA methylation seems insufficient to explain the complex pattern of tissue specificity, suggesting that DNA modification other than, or in addition to, methylation may be responsible.

Animals↗
PubMed1988

Intestinal first-pass metabolism of nitrosamines. 2. Metabolism of N-nitrosodibutylamine in isolated perfused rat small intestinal segments.

In a previous study a high first-pass metabolism of N-nitro-sodi-[1-14C]butylamine (NDBA, 0.32-730 microM) has been shown in isolated perfused rat small intestinal segments. In the present work the identification and quantitation of metabolites in samples of perfusate and absorbed fluid (absorbate) is reported. After HPLC enrichment and purification five metabolites could be identified by GLC-MS: N-nitrosobutyl-(3-hydroxybutyl)amine (NB3HBA), N-nitrosobutyl-(4-hydroxybutyl)amine (NB4HBA), N-nitrosobutyl-(3-carboxypropyl)amine (NB3CPA), N-nitrosobutyl-(2-hydroxy-3-carboxypropyl)amine (NB2H3CPA) and N-nitrosobutylcarboxymethylamine (NBCMA), representing greater than 95% of total metabolites. omega-hydroxylation leading to NB4HBA and NB3CPA accounted for 75-95% of total metabolites. The formation of their follow-up products NB2H3CPA and NBCMA was too small for quantitative analysis. In absorbate NB3CPA was by far the most important metabolite. The hydroxylation of NB4HBA to NB3CPA was more efficient in jejunal as compared to ileal segments. omega-1-hydroxylation to NB3HBA and, as reported previously, alpha-hydroxylation were only minor metabolic pathways. In conclusion, a high first-pass metabolism of NDBA to the proximate bladder carcinogen NB3CPA takes place during its absorption in rat small intestine. This is in contrast to the observation in rat liver preparations, where alpha- and omega-1-hydroxylation are the predominant pathways. The intestinal first-pass metabolism may play a key role explaining the increased incidence of bladder tumors in rats after low oral doses of NDBA.

Animals↗
PubMed1988

Intestinal first-pass metabolism of nitrosamines. 3. Identification of metabolites of N-nitrosodiamylamine.

In a previous study a high first-pass metabolism of N-nitrosodi-[1-14C]amylamine (NDAA, 0.59-350 microM) has been shown in isolated perfused rat small intestinal segments. In the present work the identification of metabolites in samples of perfusate and absorbed fluid (absorbate) is reported. After HPLC enrichment and purification five metabolites could be identified by GLC-MS which are the result of omega- and omega-1-hydroxylation, N-nitrosoamyl-(5-hydroxyamyl)amine (NA5HAA), N-nitrosoamyl-(4-hydroxyamyl)amine (NA4HAA), N-nitrosoamyl-(4-oxoamyl)amine (NA4OAA), N-nitrosoamyl-(4-carboxybutyl)amine (NA4CBA), and N-nitroso-amyl-(2-carboxyethyl)amine (NA2CEA). In rat urine the presence of only two of these metabolites, NA4HAA and NA2CEA, has been reported in the literature.

Animals↗
PubMed2004

Stereoselective metabolism and tissue retention in rats of the individual enantiomers of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), metabolites of the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK).

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is reduced to its main metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in a reaction that is both stereoselective and reversible. (S)-NNAL has been shown to be equivalent to NNK in carcinogenic potency, and significantly more potent than (R)-NNAL. It was hypothesized that stereoselective differences in metabolism or tissue distribution contributed to the difference in carcinogenicity between the enantiomers. The individual NNAL enantiomers were therefore administered to bile duct-cannulated rats. Male Fisher F344 rats received i.v. doses of either (R)-NNAL (n = 10) or (S)-NNAL (n = 9) and bile, urine, blood and tissue samples were collected over 24 h. (R)/(S)-NNAL and metabolites were quantified by HPLC and radioflow detection. NNAL was also collected from the HPLC and silylated, and the two NNAL enantiomers were separated by chiral GC-TEA. (S)-NNAL had a much larger tissue distribution (Vss = 1792 +/- 570 ml) than did (R)-NNAL (Vss = 645 +/- 230 ml). Overall, (R)-NNAL tended to enter detoxification pathways, particularly glucuronidation, while reversible metabolism of (S)-NNAL to NNK was favored. For example, after (R)-NNAL administration, approximately 50% of the dose was excreted as (R)-NNAL-Gluc in bile and urine, and <5% was excreted as NNK or NNK metabolites. In contrast, only 10% of an (S)-NNAL dose was excreted as a glucuronide, while almost 20% of the (S)-NNAL dose was excreted as NNK or NNK metabolites. In tissues, particularly the lung, (S)-NNAL appeared to be stereoselectively retained. These findings suggest that the difference in carcinogenicity between the NNAL enantiomers may be attributed to stereoselective differences in tissue distribution and excretion.

Animals↗
PubMed1975

Effect of beta-oxidized nitrosamines on syrian hamsters. III. 2,2'-Dihydroxydi-n-propylnitrosamine.

2, 2-Dihydroxy-di-n-propylnitrosamine (DHPN), an assumed metabolite of di-n-propylnitrosamine (DPN), injected subcutaneously once weekly for life, was carcinogenic in Syrian hamsters. The main target organs were the respiratory tract, pancreas, liver, and kidneys. In the respiratory system the most affected segments were the nasal cavities and the lungs. Adenomas and adenocarcinomas, mostly of ductal origin, were induced in the pancreas. Liver neoplasms were hemangloendotheliomas, angiosarcomas, hepatocellular adenomas, cholangiomas, and cholangiocarcinomas. Kidney neoplasms were adenomas and adenocarcinomas. The morphology of the induced neoplasms was described, as well as the effects of DHPN, compared to those another possible metabolite of DPN, 2-hydroxypropyl-n-propylnitrosamine (2-HPPN), which is formed in vivo with only 1 aliphatic chain degraded via theta-oxidation.

Adenocarcinoma↗
PubMed1977

Kinetics of nitrosamine formation in the presence of micelle-forming surfactants.

The nitrosation of dihexylamine by nitrite was catalyzed in the presence of micelles of the cationic surfactant decyltrimethylammonium bromide. Rate enhancements up to 800-fold were observed. The magnitude of the rate enhancements was dependent on the amine structure, particularly the alkyl chain length. Rate enhancements for nitrosation were also observed in the presence of micelles of phosphatidylcholine and Triton X-100. We present a mechanistic interpretation of these catalytic effects.

Catalysis↗
PubMed1997

Nutritional factors in the etiology of brain tumors: potential role of nitrosamines, fat, and cholesterol.

Several possible risk factors for brain tumors have been suggested in the past, including N-nitroso compounds, but with the exception of ionizing radiation, none has been consistently confirmed. The present study was aimed at assessing the influence of nutritional factors, including N-nitroso compounds, in the etiology of brain tumors, specifically gliomas and meningiomas. One hundred and thirty-nine cases with confirmed brain tumors diagnosed between 1987 and 1991 in central Israel and 278 controls matched according to age, sex, and ethnic origin were interviewed. Nutritional data were obtained using a semiquantitative food frequency approach. A significant positive association for both types of brain tumors was found with high protein intake (odds ratio (OR) = 1.94, 95% confidence interval (CI) 1.03-3.63), while intake of sodium was inversely related to both types of brain tumors (OR = 0.52, 95% CI 0.31-0.87). Increased consumption of total fat and cholesterol was inversely related to gliomas (high intake of fat: OR = 0.45, 95% CI 0.20-1.07; high intake of cholesterol: OR = 0.38, 95% CI 0.14-1.01). However, neither fat intake nor cholesterol intake was significantly related to the risk of meningiomas. Although N-nitroso compounds were not found to be directly associated with brain tumors, the data suggested the presence of an interaction between the effects of N-nitroso compounds and protein intake and between N-nitroso compounds and cholesterol intake. The data suggest that dietary factors may play an important, though yet undefined, role in the development of brain tumors.

Adolescent↗
PubMed1988

Nitrosamine formation by denitrifying and non-denitrifying bacteria: implication of nitrite reductase and nitrate reductase in nitrosation catalysis.

Biochemical, microbiological and genetic studies were done to characterize the mechanism of bacterial formation of N-nitrosomorpholine (NMOR) from morpholine and nitrite at neutral pH. In Escherichia coli and Proteus morganii, the nitrosating activity was markedly induced when bacteria were cultured under anaerobiosis in minimal medium containing nitrate, while in the presence of nitrite there was no induction. However, induction of the nitrosating activity in Pseudomonas aeruginosa occurred in anaerobic cultures in the presence of either nitrate or nitrite. The nitrosation capacity was also examined in various E. coli K12 mutants whose structural gene of either nitrate reductase or nitrite reductase was deleted. Nitrosation was not linked to the three (NADH-, formate- and glucose-dependent) nitrite reductases but was directly dependent on the presence of a nitrate reductase.

Escherichia coli↗
PubMed2006

Lung as a new target in rats of 2-amino-3-methylimidazo[4,5-f]quinoline carcinogenesis: results of a two-stage model initiated with N-bis(2-hydroxypropyl)nitrosamine.

The effects of IQ on the promotion stage of DHPN-induced lung carcinogenesis and contributions of oxidative stress were investigated in rats. Groups of 20 male 6-week-old F344 rats were given 0.1% DHPN in their drinking water for 2 weeks for initiation. From the age of 9 weeks, they were treated with 0, 150 and 300 p.p.m. of IQ in the diet for 27 weeks. Control rats were similarly fed 300 p.p.m. IQ or basal diet alone without the preceding initiation. IQ clearly (P < 0.01) enhanced the multiplicity of lung tumors in a dose-dependent manner (DHPN alone, 3.63 +/- 1.80; DHPN +150 p.p.m. IQ, 11.50 +/- 5.04; DHPN +300 p.p.m. IQ, 18.83 +/- 4.58 [no./rat]). In addition, the incidence of lung tumors in the 300 p.p.m. IQ alone group (25%) was significantly (P < 0.05) higher than that in the non-treatment group (0%). In a second experiment, male rats were given IQ at doses of 0 and 300 p.p.m. in the diet for one week in order to analyze 8-OHdG formation, levels of TBARS and BrdU-LI in the lungs. There were no changes in 8-OHdG or TBARS levels, but significant elevation of BrdU-LI occurred in the IQ administration group. The overall data clearly indicate that IQ is a potent lung carcinogen in rats, in which oxidative stress may not be involved in lung carcinogenesis.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2006

Modification by curcumin of mutagenic activation of carcinogenic N-nitrosamines by extrahepatic cytochromes P-450 2B1 and 2E1 in rats.

To elucidate the mechanism underlying suppression by curcumin of esophageal carcinogenesis induced by NMBA, we evaluated the CYP level and mutagenic activation of environmental carcinogens, by immunoblot analyses and Ames preincubation test, respectively, and bilirubin, 4-nitrophenol and testosterone UDPGT activities in F344 rats treated with curcumin and/or NMBA. No significant alterations in the hepatic levels of constitutive CYP proteins, mutagenic activation by liver S9 or hepatic UDPGT activities were produced by subcutaneous treatment with 0.5 mg/kg NMBA for 5 weeks and/or feeding of 0.05% and 0.2% curcumin for 6 weeks. In contrast, gavage of 0.2% curcumin decreased esophageal CYP2B1 and 2E1 by up to 60%, compared with vehicle control. Similarly, intragastric treatment with 270 mg/kg curcumin decreased esophageal and gastric CYP2B1 and CYP2E1, but not in lung, kidney or intestine. Conversely, large intestinal CYP2B1 was 2.8-fold higher in the treated rats than in control rats. Mutagenic activities of NOC, including NMBA, in the presence of esophagus and stomach S9 were markedly decreased in the treated rats, whereas those in the presence of large intestine S9 were 2.2-3.0-fold above control. These results show that modifying effects of curcumin on esophageal carcinogenesis can be attributed to a decrease in metabolic activation of NMBA by esophageal CYP2B1 during the initiation phase, without the contribution of metabolic activation and inactivation by liver. Further, the present findings suggest the potential of curcumin for modification of gastric and intestinal carcinogenesis initiated with NOC.

Animals↗