sodium-nitrite and dimethylamine

1. Dimethylamine borane (DMAB) is used as a reducing agent in the manufacturing of a variety of products and in chemical synthesis. National Toxicology Program is evaluating the toxicity of DMAB in rodents following dermal application. The objective of this study was to evaluate the metabolism and disposition of DMAB in male Harlan Sprague Dawley (HSD) rats. 2. Disposition of radioactivity was similar between gavage and intravenous administration of 1.5 mg/kg [(14)C] DMAB, with nearly 84%-89% of the administered radioactivity recovered in urine 24 h post dosing. At 72 h, only 1% or less was recovered in feces, 0.3% as CO2, and 0.5%-1.4% as volatiles and 0.3%-0.4 % in tissues. 3. The absorption of [(14)C]DMAB following dermal application was moderate; percent dose absorbed increased with the dose, with 23%, 32% and 46% of dose absorbed at 0.15, 1.5 and 15 mg/kg, respectively. Urinary and fecal excretion ranged from 18%-37% and 2%-4% of dose, respectively, and 0.1%-0.2% as CO2, and 1%-3% as volatiles. Tissue retention of the radiolabel was low ∼1%, but was higher than following the gavage or intravenous administration. 4. Following co-adminsitration of DMAB and sodium nitrite by gavage, N-nitrosodimethylamine was not detected in blood or urine above the limit of quantitation of the analytical method of 10 ng/mL. 5. Absorption of DMAB in fresh human skin in vitro was ∼41% of the applied dose: the analysis of the receptor fluid shows that the intact DMAB complex can be absorbed through the skin.

Topics: Administration, Cutaneous; Administration, Intravenous; Animals; Boranes; Carbon Radioisotopes; Dimethylamines; Dimethylnitrosamine; Feces; Humans; Male; Rats; Rats, Sprague-Dawley; Sodium Nitrite

The study involved two groups of patients aged 6-14 and 40-60 years, and identification of different conditions of gastric mucosa. The study has established a correlation between the nitrosation activity and acidity of gastric juice and the pathological condition of the gastric mucosa. Enhanced nitrosation activity was observed in samples with a pH under 4.0. That activity was at its lowest in cases of normal gastric mucosa, and at its peak--in high-acidity superficial and erosive gastritis. In cases of superficial gastritis with similar levels of acidity, the nitrosation activity of gastric juice for different amines in children was 2-4 times that in adults. The difference in nitrosation levels for different amines tended to diminish with the decrease in the basicity of the amine in question. A linear correlation was observed between the free-radical activity of gastric juice samples and nitrosation activity (correlation coefficient, k = 0.72).

Topics: Adolescent; Adult; Aging; Child; Dimethylamines; Free Radicals; Gastric Acidity Determination; Gastric Juice; Gastric Mucosa; Humans; Hydrogen-Ion Concentration; Middle Aged; Nitrosation; Sodium Nitrite; Stomach Diseases

The study was concerned with evaluation of the effect of human gastric juice (samples obtained from 157 subjects) on in vitro dimethylnitrosamine nitrosation by sodium nitrite versus gastric mucosa pathology (gastritis, polyps, ulcer, cancer), gastric juice pH and nitrate ion level. Also, the influence of gastric juice glycosaminoglycans and glycoproteins levels as well as N-acetylneuraminic acid isolated from porcine blood was assessed. An increased nitrosating activity of gastric juice was observed in cases of gastritis and ulcer and in those with low nitrate ion activity. Glycosaminoglycans and glycoproteins were found to inhibit nitrosation. N-acetylneuraminic acid in the concentrations used exerted no effect on dimethylnitrosamine nitrosation by sodium nitrite.

Topics: Dimethylamines; Gastric Juice; Glycoproteins; Glycosaminoglycans; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Nitrites; Nitroso Compounds; Sodium Nitrite; Stomach Diseases

The article deals with a comparison of the results of human body nitrosating ability determination by two methods: (a) nitroso compound (NC) assay in diurnal urine after oral administration of its precursors, and (b) assay of the same in gastric juice after in vitro addition of precursors. The data for the first part of the investigation were obtained from the literature, and for the second one--from the experiments by the authors. Both studies used essentially identical groups of patients, primarily those suffering gastrointestinal pathology. Since the results matched to a considerable degree, it was inferred that (1) gastric juice is a factor of body nitrosating ability, and (2) in vitro determinations of said ability in gastric juice are fully justified. Moreover, the latter procedure is sometimes more practicable, particularly, in view of the marked relationship between nitrosating ability, and, especially, the efficacy of inhibitors of NC endogenous synthesis, on the one hand, and the individual characteristics of the body, on the other.

Topics: Aminopyrine; Dimethylamines; Fasting; Gastric Acidity Determination; Gastric Juice; Humans; Hydrogen-Ion Concentration; In Vitro Techniques; Methods; Morpholines; Nitrates; Nitrosamines; Nitroso Compounds; Proline; Sodium Nitrite

The simultaneous administration of 14C-dimethylamine and sodium nitrite to rat stomach produces the formation of O6-methylguanine and 7-methylguanine in the liver DNA as a result of the endogenic synthesis of N-nitrosodimethylamine (NDMA). Methylation of DNA was also observed in the rat kidney and lung. Alkylation of O6-position of guanine and removal of its methylated product from the DNA occurred in the liver to a greater extent than in the other NDMA target organs. Pretreatment of rats with sodium nitrite increased the alkylation of liver DNA caused by endogenic synthesis of NDMA. The formation of alkylated products in DNA may be used as a marker for the endogenic formation of NDMA from precursors.

Topics: Alkylation; Animals; Dimethylamines; Dimethylnitrosamine; DNA; DNA Damage; Guanine; Kidney; Liver; Lung; Male; Rats; Sodium Nitrite

The damage of liver DNA formation during endogenic synthesis of N-nitrosodimethylamine (NDMA) have been studied after introduction of its precursors, dimethylamine, amidopyrine and sodium nitrite, into the rat stomach. A combined administration of various doses of dimethylamine and nitrite increased the amount of single-strand DNA from 3.0 to 11.3%. The maximum DNA damage after administration of the precursors was observed after 24 h, and after 48 h it decreased to the control level. Pretreatment of rats with dimethylamine or nitrite increased the DNA damage induced by NDMA formation (37.4% and 41.6%, respectively).

Topics: Alkylation; Aminopyrine; Animals; Dimethylamines; Dimethylnitrosamine; DNA; DNA, Single-Stranded; Dose-Response Relationship, Drug; Liver; Male; Rats; Sodium Nitrite; Time Factors

The study was concerned with a comparison of the effects of ethanol on N-nitrosodimethylamine (NDMA) synthesis from amidopyrine and sodium nitrite in rat stomach and on the same synthesis from dimethylamine (DMA) and sodium nitrite involving a 30-min incubation of their mixture at 37 degrees C in acid medium. Alcohol was found to inhibit DMA nitrosation thus lowering the yield of NDMA both in rat stomach and in a medium containing human gastric juice or glycine-hydrochloride buffer (pH = 3.4).

Topics: Animals; Biotransformation; Chemical Phenomena; Chemistry; Depression, Chemical; Dimethylamines; Dimethylnitrosamine; Ethanol; Gastric Juice; Intestinal Absorption; Mice; Sodium Nitrite; Tissue Distribution

We have demonstrated that there is a dose-related increase in the excretion of 7-[methyl-14C]methylguanine ( [14C]m7Gua) following p.o. administration of di[methyl-14C]methylnitrosamine to rats. Urine was collected for 24 hr after di[methyl-14C]methylnitrosamine administration, and the purines were precipitated from an aliquot of the urine with silver nitrate. Purines were released from the precipitate with HCl, and [14C]m7Gua was quantified by chromatography on an Aminex A-6 column. The excretion of [14C]m7Gua increased linearly with the dose of dimethylnitrosamine. This relationship was used to estimate the amount of di[methyl-14C]methylnitrosamine formed in the reaction of [14C]aminopyrine with sodium nitrite in rats gavaged with these compounds. The dose of dimethylnitrosamine was also estimated from the amount of alkylation of liver DNA in the same animals. These estimates usually differed by less than a factor of 2. [14C]aminopyrine and sodium nitrite were administered. The possibility of using this assay to obtain data on nitrosation in humans is discussed.

Topics: Aminopyrine; Animals; Carbon Radioisotopes; Dimethylamines; Dimethylnitrosamine; DNA; Guanine; Kinetics; Liver; Male; Nitrites; Rats; Rats, Inbred Strains; Sodium Nitrite

It is known that sodium nitrite and dimethylamine are toxic compounds, which may react to form dimethylnitrosamine in the gastro-intestinal tract, a much more toxic compound and a powerful cancerogen. The aim of the present work is the investigation of toxicity in young rats, caused by daily intake of sodium nitrite, administered together with dimethylamine during 30 days. The indicators examined were: histopathological analysis of the liver and kidney, transaminase in blood serum, variations in body weight and relation of weight liver/body weight. The method of analysis used to determine transaminase was that reported by Reintman and Frankel in 1957. The statistical method employed was the test of multiple comparisons based on the total ranges of Cruskal-Wallis. The results show that either significant differences were found (alpha = 0,05) among the groups (including the control), nor was necrosis observed or forming of tumors in the organs under investigation. Therefore, the doses administered does not seem to be toxic under the conditions of the experiment. Some signs of toxicity found in the group which was severely treated (10 mg of sodium nitrite and 20 mg of dimethylamine) appeared only in a few animals and it is necessary to verify the same in experiments with more animals and over a longer period of treatment.

Topics: Alanine Transaminase; Animals; Body Weight; Dimethylamines; Dose-Response Relationship, Drug; Kidney; Liver; Male; Nitrites; Organ Size; Rats; Rats, Inbred Strains; Sodium Nitrite

The influence of intestinal microflora on the hepatotoxic effects of dimethylnitrosamine (DMN) or dimethylamine (DMA) plus NaNO2 was studied by comparing the degree of liver necrosis and the levels of serum alanine aminotransferase (GPT) and aspartate aminotransferase (GOT) in germ-free and conventional male Wistar rats (320 to 340 g). In one experiment, both germ-free and conventional rats were intubated with DMN in respective doses of 8, 9, and 10 mg/kg of body weight, while in another experiment, both groups were intubated with DMA (1500 mg/kg) plus NaNO2 (100 mg/kg). In both experiments, 48 hr after intubation, there was a marked difference in the degree of liver necrosis and the levels of serum GPT and GOT between the groups. In particular, a dose of 8 mg of DMN or 1500 mg of DMA plus 100 mg of NaNO2 produced severe liver necrosis in the majority of germ-free rats, while the same dose did not produce any detectable liver necrosis in the majority of conventional rats. At a dose of 8 mg, serum GPT and GOT levels were raised to 22 and 15 times normal values, respectively, in germ-free rats, but only to about twice the normal values for both levels in conventional rats. At the combination dose of DMA plus NaNO2, the levels of serum GPT and GOT were raised to 40 and 30 times normal values, respectively, in germ-free rats, while both levels remained almost normal in conventional rats. Thus, the results indicated that the liver of the germ-free state was far more susceptible to the acute toxic effects of DMN as well as DMA plus NaNO2 administration at a certain dose range than was the liver of the conventional state, suggesting the influence of the absence of microflora.

Topics: Administration, Oral; Animals; Dimethylamines; Dimethylnitrosamine; Germ-Free Life; Liver; Male; Necrosis; Nitrites; Rats; Rats, Inbred Strains; Sodium Nitrite