PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “NITROSO COMPOUNDS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 19 recordsLinked to original sources
PubMed1986

[Molecular mechanisms of radiation-sensitizing effects of nitroso compounds: new approaches to the prognosis of their effectiveness].

Basing on the results of EPR investigations and an analysis of literature data an assumption was made of the new factors in the mechanism of the radiosensitizing action of nitro compounds. It was assumed that irradiation-induced accumulation of toxic products of incomplete reduction of the nitro group of these compounds--nitroso- and hydroxyl amino-derivates--in tumor hypoxic zones played the main role in the radiosensitizing action of nitro compounds.

Animals↗
PubMed1982

Influence of ascorbic acid on the endogenous (intragastral) formation of N-nitroso compounds.

N-Nitroso compounds are not only environmentally occurring carcinogens, but can also be generated in vivo from their precursors. Nitrosation rates depend on the chemical structures of the compounds to be nitrosated, their basicity, the pH value of the reaction medium and the availability of nitrosating agents. Yields of N-nitroso compounds can be enhanced by catalysts or decreased by inhibitors. One of the most potent inhibitors of N-nitrosation is ascorbic acid, which has been shown to block formation of N-nitroso compounds very effectively in vitro and also in animal experiments at high dosages; alpha-tocopherol seems to be of similar effectiveness. In the human situation, ascorbic acid can be applied to prevent nitrosamine formation in the gastrointestinal tract. However, the pharmacokinetics of the nitrosable compounds also play an important role: recirculation of drugs with long half-lives through the bloodstream via the salivary glands would need a continuous intake of ascorbic acid as long as the drug is present in the plasma, since ascorbic acid practically does not follow the blood-saliva circulation process.

Animals↗
PubMed1980

Adenosine 3',5'-monophosphate formation by preparations of rat liver soluble guanylate cyclase activated with nitric oxide, nitrosyl ferroheme, S-nitrosothiols, and other nitroso compounds.

Cyclic AMP formation from ATP was stimulated by unpurified and partially purified soluble hepatic guanylate cyclase in the presence of nitric oxide (NO) or compounds containing a nitroso moiety such as nitroprusside, N-methyl-N-nitro-N-nitrosoguanidine (MNNG), nitrosyl ferroheme, and S-nitrosothiols. Cyclic AMP formation was undetectable in the absence of NO or nitroso compounds and was not stimulated by fluoride or glucagon, indicating the absence of adenylate cyclase activity. The nitroso compounds failed to activate, whereas fluoride or glucagon activated, adenylate cyclase in washed rat liver membrane fractions. Cyclic GMP formation from GTP was markedly stimulated by the soluble hepatic fraction in the presence of NO or nitroso compounds. Cyclic AMP formation by partially purified guanylate cyclase was competitively inhibited by GTP and cyclic GMP formation is well-known to be competitively inhibited by ATP. Therefore, it appears that activated guanylate cyclase, rather than adenylate cyclase, was responsible for the formation of cyclic AMP from ATP. Formation of cyclic AMP of cyclic GMP was enhanced by thiols, inhibited by hemoproteins and oxidants, and required the addition of either Mg2+ or Mn2+. Further, several nitrosyl ferroheme compounds and S-nitrosothiols stimulated the formation of both cyclic AMP and cyclic GMP by the soluble hepatic fraction. These observations support the view that soluble guanylate cyclase is capable, under certain well-defined conditions, of catalyzing the conversion of ATP to cyclic AMP.

Adenosine Triphosphate↗
PubMed1983

Presence of N-nitroso-L-thioproline and N-nitroso-L-methylthioprolines in human urine as major N-nitroso compounds.

Unknown N-nitroso compounds were found in human urine of healthy volunteers by gas chromatography-thermal energy analysis. These compounds were identified as N-nitroso-L-thioproline and cis- and trans-N-nitroso-L-methylthioprolines by gas chromatography-mass spectrometry. The precursors of these new N-nitroso compounds may be formed by the reactions of L-cysteine with formaldehyde and acetaldehyde in the human body.

Chromatography, Gas↗
PubMed1999

N-Nitroso compounds in the diet.

N-Nitroso compounds were known almost 40 years ago to be present in food treated with sodium nitrite, which made fish meal hepatotoxic to animals through formation of nitrosodimethylamine (NDMA). Since that time, N-nitroso compounds have been shown in animal experiments to be the most broadly acting and the most potent group of carcinogens. The key role of nitrite and nitrogen oxides in forming N-nitroso compounds by interaction with secondary and tertiary amino compounds has led to the examination worldwide of foods for the presence of N-nitroso compounds, which have been found almost exclusively in those foods containing nitrite or which have become exposed to nitrogen oxides. Among these are cured meats, especially bacon-and especially when cooked; concentrations of 100 micrograms kg(-1) have been found or, more usually, near 10 micrograms kg(-1). This would correspond to consumption of 1 microgram of NDMA in a 100-g portion. Much higher concentrations of NDMA (but lower ones of other nitrosamines) have been found in Japanese smoked and cured fish (more than 100 micrograms kg(-1)). Beer is one source of NDMA, in which as much as 70 micrograms l(-1) has been reported in some types of German beer, although usual levels are much lower (10 or 5 micrograms l(-1)); this could mean a considerable intake for a heavy beer drinker of several liters per day. Levels of nitrosamines have been declining during the past three decades, concurrent with a lowering of the nitrite used in food and greater control of exposure of malt to nitrogen oxides in beer making. There have been declines of N-nitroso compound concentrations in many foods during the past two decades. The small amounts of nitrosamines in food are nonetheless significant because of the possibility-even likelihood-that humans are more sensitive to these carcinogens than are laboratory rodents. Although it is probable that alkylnitrosamides (which induce brain tumors in rodents) are present in cured meats and other potentially nitrosated products in spite of much searching, there has been only limited indirect evidence of their presence.

Beer↗
PubMed1990

Several known indole compounds are not important precursors of direct mutagenic N-nitroso compounds in green cabbage.

In this study we investigated the role of indole-3-acetonitrile, indole-3-carbinol, indole and tryptophan in the formation of N-nitroso compounds in green cabbage extracts. Green cabbage extracts were separated by gel permeation chromatography. Fractions were treated with nitrite, tested for mutagenicity and analysed for total N-nitroso content. Fractions in which spiked indole-3-acetonitrile, indole-3-carbinol, indole and tryptophan eluted appeared to be low in mutagenic activity and contained relatively small amounts of N-nitroso compounds. To detect indole compounds other than the ones used in the gel permeation chromatography experiments, high-performance liquid chromatography and gas chromatography-mass spectrometry analyses were performed of green cabbage extracts. Indole-3-carboxaldehyde was found to be the most commonly occurring indole compound, but it did not show direct mutagenic activity upon nitrite treatment. Indole-3-acetonitrile was the second most common compound; although it was mutagenic after nitrite treatment, its contribution to the mutagenicity of nitrite-treated green cabbage was roughly estimated to be only 2%. No other indole compounds were detected. From this study we conclude that neither the tested indole compounds nor indole-3-carboxaldehyde play a significant role in the formation of direct mutagenic N-nitroso compounds in nitrite-treated green cabbage extracts.

Brassica↗
PubMed1994

N-nitroso compounds, nitrite and pH in human fasting gastric juice.

Total N-nitroso compounds, ethyl acetate-extractable N-nitroso compounds and nitrite were measured in 146 samples of fasting gastric juice to investigate their relationship with pH. A positive correlation was found between pH and extractable N-nitroso compounds (r = 0.206, P < 0.02), whereas total N-nitroso compounds were pH-independent. It was inferred that pre-cancerous conditions associated with high gastric pH may be produced by an increase in the extractable N-nitroso compounds, which constitute only a small fraction of the total gastric N-nitroso compounds.

Adult↗
PubMed1984

Relation between gastric histology and gastric juice pH and nitrite and N-nitroso compound concentrations in the stomach after surgery for duodenal ulcer.

Formation of N-nitroso compounds in gastric juice has been implicated in the pathogenesis of cancer in the stomach after operation. Gastric juice was aspirated from 85 subjects: 23 were controls, 51 had previously undergone vagotomy and gastrojejunostomy, and 11 had previously undergone vagotomy and pyloroplasty. The gastric juice samples were analysed for pH, nitrite, and total N-nitroso compounds. A significant correlation was found between pH and nitrite concentration (p less than 0.01). No significant correlation was found between pH and total N-nitroso compound concentration or between nitrite and N-nitroso compound concentration. The vagotomy and gastrojejunostomy patients had higher pH values and higher concentrations of nitrites and N-nitroso compounds than controls (p = 0.01 in all cases). The 51 vagotomy and gastrojejunostomy patients also underwent endoscopy and biopsy. They were divided into three groups: group 1 (21 patients) had no intestinal metaplasia and no more than mild dysplasia; group 2 (20 patients) had intestinal metaplasia; and group 3 (10 patients) had moderate or severe dysplasia. Groups 2 and 3 both had higher pH values and higher nitrite concentrations than group 1 (p = 0.01 in all cases). There was no significant difference, however, between either group 2 or 3 and group 1 for total N-nitroso compound concentration. Since there was no simple linear relation between pH and N-nitroso compound concentration, it was concluded that formation of N-nitroso compounds at high pH was unlikely to be involved in the pathogenesis of gastric cancer in the hypochlorhydric stomach after operation. The relation between nitrite and histological abnormality was not associated with a similar relation between N-nitroso compounds and histological abnormality. It therefore appears that there is no simple relation between N-nitroso compounds and the pathogenesis of premalignant gastric mucosal changes.

Duodenal Ulcer↗
PubMed1980

Significance of in vivo formation of N-nitroso compounds.

Formation of N-nitroso compounds from amines and nitrite has been demonstrated in chemical systems and in the stomach of animals in vivo. The amines differ in the extent to which they give rise to N-nitroso compounds. Many amines are common in the environment. Other amines are ingested as drugs, food additives or as trace contaminants of food with agricultural chemicals. At least 20 such amines have been given chronically to rats together with sodium nitrite and the incidence of tumors compared with that in rats given the amine or nitrite alone. Until now 13 of these amines have given rise to a significant incidence of tumors under these conditions, indicating that ingestion of these amines when nitrite is present could provide a source of carcinogenic nitrosamines for man. some of the amines were more effective in this respect than others. These were aminopyrine, morpholine, disulfiram, methylbenzylamine and heptamethyleneimine.

Amines↗
PubMed1982

Vasodilator actions of several N-nitroso compounds.

Recent studies have shown that N-nitroso compounds can activate arterial guanylate cyclase and relax isolated arterial smooth muscle; however, the effects of these substances on the cardiovascular system in the anesthetized cat are unknown. The present study was undertaken to compare the effects of several nitrosoguanidines and a nitrosamine, N-nitrosodimethylamine, on arterial guanylate cyclase activity, isolated arterial smooth muscle tone, and systemic vascular resistance in the anesthetized cat. Intravenous injections and infusions of the nitrosoguanidines glyceryl trinitrate (GTN) and sodium nitroprusside (SNP) decreased systemic arterial pressure. During intravenous infusion of the nitrosoguanidines GTN and SNP, cardiac output was unchanged at the peak of the decrease in aortic pressure, indicating that the nitrosoguanidines GTN and SNP both reduced systemic vascular resistance. In addition, intraarterial injections of the nitrosoguanidines produced dose-dependent decreases in perfusion pressure in the feline mesenteric vascular bed perfused at constant flow. These substances were potent relaxants of isolated arterial smooth muscle and markedly activated arterial guanylate cyclase. In contrast, N-nitrosodimethylamine was devoid of vasodilator activity in vivo and exerted only minimal effects on isolated arterial smooth muscle tone or on arterial guanylate cyclase activity. The present data demonstrate a relationship between guanylate cyclase activation and arterial smooth muscle relaxation and suggest that the vasodilator effects on resistance vessels in vivo in response to selected N-nitroso compounds may involve such a mechanism. Although the significance of the presently reported cardiovascular responses to N-nitroso compounds is uncertain, N-nitroso compounds may represent a previously unrecognized class of substances which can be formed in the body and which possess marked vasodilator activity. It is possible that this vasodilator activity may involve the relaxation of vascular smooth muscle through activation of guanylate cyclase.

Animals↗
PubMed1997

Salivary nitrate, nitrite and N-nitroso compounds in patients with cancer of the upper aerodigestive tract.

N-nitroso compounds are carcinogens that can be ingested directly or synthesized from nitrites and nitrates. The possible role of N-nitroso compounds in the induction of upper aerodigestive tract tumours was considered in a case-control study conducted in the Valle d'Aosta, an Italian region with a high incidence of these neoplasms. Nitrate, nitrite, labile and stable N-nitroso compounds were analysed in the saliva of 36 patients with cancers of the upper aerodigestive tract and 23 healthy individuals. After allowing for tobacco, salivary nitrate, nitrite and N-nitroso compounds were not associated with an increased risk of upper aerodigestive tract cancers. The odds ratio for continuous units of total N-nitros compounds was 0.99 (95% confidence interval 0.9-1.1). Thus, salivary nitrate, nitrite and N-nitroso compounds might not be suitable markers for the assessment of the risk of cancer of the upper aerodigestive tract, although a role for N-nitroso compounds cannot be excluded.

Adult↗
PubMed1989

N-nitroso compound formation in human gastric juice.

The gastric formation of N-nitroso compounds probably constitutes a major source of human exposure to this important class of environmental carcinogens. Following reduction of nitrate to nitrite by oral or gastric bacteria, reaction with nitrogenous constituents of gastric juice can occur leading to the in situ formation of N-nitroso compounds, probably primarily derived from amides, ureas or aromatic amines. While gastric nitrite concentrations are raised in the achlorhydric relative to the normal stomach, the latter, owing to its acidity, offers a particularly favourable environment for the formation of N-nitroso compounds, as indicated by the finding of greatly increased gastric concentrations of N-nitroso compounds following an oral dose of nitrate. This illustrates the importance of the dynamic nature of the relationships between the various parameters involved in the formation of N-nitroso compounds. While in principle the same is true of the process of inhibition of nitrosation by reducing agents such as ascorbic acid (since, depending on the relative concentrations of reducing agent, nitrite and oxygen, inhibition or catalysis of nitrosation can occur), ingestion of 1 g ascorbic acid brings about a significant reduction in the gastric concentration of N-nitroso compounds.

Animals↗
PubMed1989

Environmental exposure to preformed nitroso compounds.

In the human environment, nitrosatable amine precursors to N-nitroso compounds and nitrosating species such as nitrite and oxides of nitrogen are abundant. As a result, the formation of N-nitroso compounds and human exposure to these compounds show a rather complex pattern. The largest known human exposures to exogenous N-nitrosamines occur in the work place. This is particularly evident in the rubber and tyre manufacturing industry and in metal cutting and grinding shops. Nearly all industries which are concerned with the production and/or use of amines have a related nitrosamine problem. Outside the industrial environment, commodities such as cosmetics, pharmaceuticals, rubber and household products, which are either prepared from amines or contain high concentrations of amino compounds, may be subject to contamination by low concentrations of N-nitroso compounds. This contamination may result from the use of contaminated starting materials, in particular amines, or from the formation of N-nitroso compounds during manufacturing processes. A similar problem exists with agricultural chemicals. As our knowledge of the occurrence and formation of N-nitroso compounds in the environment increases, preventive measures can be introduced, particularly in manufacturing industries, to reduce the levels of human exposure to nitrosamines in the work place and to protect the consumer from nitrosamine exposure from household commodities.

Air Pollution↗
PubMed1988

Intestinal cancer induced by N-nitroso compounds.

Several N-nitroso compounds induce tumors of the colon, and some induce tumors in other parts of the intestinal tract as well. The nitrosamines that induce colon tumors are beta oxidized n-propyl-nitrosamines. These require metabolic activation, as do 1,2-dimethylhydrazine, azomethane, and azoxymethane, another group of colon carcinogens. Several nitrosoalkylureas induce tumors in rat colons after oral administration, although the monoalkylnitrosoureas are fairly unstable and might not be expected to reach the colon. However, monoalkylnitrosoureas are equally effective with the much more stable dialkylnitrosoureas. Although nitrosomethylurea did not induce colon tumors under these conditions, nitrosoethylurea did, together with nitrosodiethylurea and other nitrosoethylalkylureas. Nitroso-n-butyl-, n-amyl-, n-hexyl-urea, and nitrosohydroxyethylurea also induced colon tumors, but the last, like nitrosoethylurea, also induced tumors of the duodenum and ileum. In most of these experiments male rats were more susceptible to induction of intestinal tumors than female rats. An explanation for the differences between these compounds of similar structure might be found in variations in their ability to alkylate DNA in intestinal cells, or in differences in stability of the alkylated product between the compounds. The physical properties of the compounds might also modulate the process of carcinogenesis, however.

Alkylation↗