Disease relevance of nitrous amide

• Nitrosamine-induced transplantable pancreatic ductal adenocarcinoma in inbred Syrian hamsters [1].
• The etiology of gastric cancer. Intragastric nitrosamide formation and other theories [2].
• Nitrosamine-treated hamsters also demonstrate pulmonary neuroendocrine cell apoptosis in situ during the same time period as expression of the endogenous HGFL/ MSP gene, immediately preceding the spontaneous regression of neuroendocrine cell hyperplasia [3].
• Studies with oxidized derivatives of N-nitrosodi-n-propylamine suggested a structure-activity relationship between pancreatic cancer induction in Syrian hamsters and position and degree of nitrosamine oxidation [4].
• These data indicate that POH has a weakly promoting effect early in nitrosamine-induced esophageal tumorigenesis and suggest that POH may not be an effective chemopreventive agent for esophageal cancer in humans [5].

Psychiatry related information on nitrous amide

• The effects of chronic alcohol consumption on nitrosamine metabolism in vivo, DNA synthesis and repair, and carcinogen-induced preneoplasia were studied in rat liver [6].
• This test, which monitors 24-hr-excretion of urinary N-nitrosamino acids, is now applied in clinical and field studies, with the aim of measuring nitrosamine exposure and of identifying dietary, life-style, and host factors, or disease states, that affect nitrosation in man [7].
• OBJECTIVE: To predict the impact on tobacco use in the US of a "harm reduction" policy that requires that the smokeless tobacco product meet low nitrosamine standards, but could be marketed with a warning label consistent with the evidence of relative health risks [8].

High impact information on nitrous amide

• We differentially screened a chromosome 3 library using nitrosamine-treated versus normal hamster lung cDNAs and identified hepatocyte growth factor-like/macrophage-stimulating protein (HGFL/MSP) in injured lung [3].
• Urinary bladder tumors were induced in female Wistar rats by oral administration of N-butyl-N-(4-hydroxybutyl) nitrosamine [(BBN) CAS: 3817-11-6] [9].
• The purpose of these studies was to determine a) whether epithelial cells with altered in vitro growth capacity occur not only after topical application of 7-12-dimethylbenz [a]-anthracene but also after systemic administration of a carcinogenic nitrosamine, and b) whether such cells can be isolated from tissues other than tracheal mucosa [10].
• Kinetics of nitrosamine formation in the presence of micelle-forming surfactants [11].
• Effect of cimetidine on gastric juice N-nitrosamine concentration [12].

Chemical compound and disease context of nitrous amide

• These results demonstrate for the first time a relation between gastric juice N-nitrosamine concentration, pH, and cimetidine treatment, and the findings are discussed in relation to gastric cancer induction [12].
• The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent pulmonary carcinogen in laboratory animals and is most likely involved in the etiology of tobacco smoke-induced lung cancer [13].
• Nitrite and nitrosamine synthesis by hepatocytes isolated from normal woodchucks (Marmota monax) and woodchucks chronically infected with woodchuck hepatitis virus [14].
• HPV-16, tobacco-specific N-nitrosamine, and N-methyl-N'-nitro-N-nitrosoguanidine in oral carcinogenesis [15].
• Nitrosohydroxyethylurea and the related cyclic nitrosamide, nitrosooxazolidone, were as potent as nitrosoethylurea as skin carcinogens, although the latter was a much weaker mutagen to Salmonella [16].

Biological context of nitrous amide

• Thiocyanate was also found in all specimens in concentrations likely to increase nitrosamine formation, if nitrosation of amines occurs in the fasting stomach [17].
• Our data suggest that nicotine can potentially interfere with the carcinogenicity of NNK by competition for enzyme systems essential for the metabolic activation of the nitrosamine and by competition as ligand for nicotinic cholinergic receptors [18].
• Angiotensin II type 2 receptor gene deficiency attenuates susceptibility to tobacco-specific nitrosamine-induced lung tumorigenesis: involvement of transforming growth factor-beta-dependent cell growth attenuation [19].
• Methyl-3,4-dichlorophenyl thioether was detected, but the quantities found were not significantly different from the background levels of methylation product detected in the absence of nitrosamine [20].
• Epidemiological studies in China suggest that dietary zinc deficiency and environmental exposure to N-nitrosamine carcinogens, such as N-nitrosomethylbenzylamine (NMBA), are among the factors associated with an increased incidence of esophageal carcinoma in humans [21].

Anatomical context of nitrous amide

• A tobacco-specific N-nitrosamine or cigarette smoke condensate causes neoplastic transformation of xenotransplanted human bronchial epithelial cells [22].
• These observations, together with the available data on carcinogenicity of the nitrosamine in the rat and rabbit, suggest that in the esophagus, at least, metabolic activation of NMBZA is necessary to elicit its toxic and/or carcinogenic effect [23].
• High-affinity nitrosamine dealkylase system in rat liver microsomes and its induction by fasting [24].
• 4-(N-Methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a major nitrosamine formed in tobacco smoke, induces a high incidence of lung, liver, and nasal cavity tumors in rats [25].
• Using a method for nitrosamine analysis that gives high recovery values and that is free from artifactual synthesis of nitrosamines, we have shown that human feces do not contain volatile nitrosamines (detection limit, 0.1 to 0.5 microgram/kg) [26].

Associations of nitrous amide with other chemical compounds

• Treatment of nitrosamine-induced pancreatic tumors in hamsters with analogs of somatostatin and luteinizing hormone-releasing hormone [27].
• We have previously shown that the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is an active transplacental carcinogen in Syrian golden hamsters when administered by s.c. injections to pregnant females [28].
• On the other hand, quantitative differences in the genotoxic effects induced by 5 mM N-nitrosodimethylamine in cultures derived from 20 human donors and from 20 rats were greater than average interspecies differences displayed by this nitrosamine and by other N-nitroso compounds [29].
• The human cytochrome P4502E1 gene (P4502E1), coding for an ethanol-inducible nitrosamine-metabolizing P-450, is involved in the metabolism of ethanol and many known carcinogens [30].
• Nitrosomethoxymethylamine was the only nitrosamine that exhibited mutagenic activity in the absence of hepatocytes, and this activity was diminished in the presence of hepatocytes [31].

Gene context of nitrous amide

• Results showed that 8 of 28 (28%) and 6 of 13 (46%) of the Fhit -/- and +/-, respectively, versus 2 of 25 (8%) Fhit +/+ mice developed invasive carcinoma after treatment with N-butyl-N-(4-hydroxybutyl) nitrosamine [32].
• The tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK) is a potential human carcinogen that is known to be metabolized to DNA-reactive intermediates by the cytochromes P450 [33].
• CYP2A6/2A7 and CYP2E1 expression in human oesophageal mucosa: regional and inter-individual variation in expression and relevance to nitrosamine metabolism [34].
• The purpose of the current investigation was to characterize the expression of p16 and p15 in lung tumors and tumor-derived cell lines induced in A/J mice by exposure to the tobacco-specific nitrosamine, 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) [35].
• The results of experiments using mice which were treated with NNK, a carcinogenic nitrosamine contained in tobacco smoke, together with 8-methoxypsolaren, a strong inhibitor of CYP2A6, indicated that the inhibition of CYP2A6 completely abolished the occurrence of adenoma [36].

Analytical, diagnostic and therapeutic context of nitrous amide

• Gas chromatography and nitrosamine-selective detection, with confirmation by mass spectrometry, were used in the analyses, which were performed without knowledge of the origin of the urine samples [37].
• The tumor, a primary one induced by chronic administration of the nitrosamine N-nitro-bis(2-hydroxyproyl) amine, is a well-differentiated adenocarcinoma that can be propagated by transplantation in syngeneic hamsters [1].
• The metabolites present in the culture media were separated by high performance liquid chromatography and were identified by comparison to standards. alpha-Hydroxylation of NNN, an esophageal carcinogen, was the major pathway for metabolism of this nitrosamine in both tissues [38].
• We conclude from these results that dithiocarbamates may be suitable compounds for chemoprevention of nitrosamine-induced tumors [39].
• Increased urinary nitrosamine excretion in patients with urinary diversions [40].

References