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S R Tannenbaum

Publications and source records attributed to S R Tannenbaum.

At least 163 records · Page 9Linked to original sources
PubMed1984

Mammalian nitrate biochemistry: metabolism and endogenous synthesis.

The metabolic fate of an oral dose of 3.5 mmol 15N-labelled nitrate was investigated in young adults. An average of 60% of the 15N-nitrate dose appeared in the urine within 48 h; less than 0.1% appeared in the faeces. Some of the 15N label of nitrate was found in the urine (3%) and faeces (0.2%) in the form of ammonia and urea; the remainder of the dose was attributed to nitrate loss via metabolism to other reduced nitrogen compounds. Studies with germ-free rats indicated that half of the nitrate metabolism is due to mammalian processes. These and previous studies show that not all of the nitrate excreted in the urine is of dietary origin but evolves from endogenous synthesis. An oral dose of 15N-ammonium acetate was incorporated into urinary 15N-nitrate in rats, suggesting that ammonia is a precursor of nitrate. Furthermore, Escherichia coli lipopolysaccharide was found to be a potent stimulus of nitrate excretion (nine-fold increase), due to an increased rate of synthesis. Two other types of experimentally induced inflammatory states - injection of carrageenan and of turpentine - enhanced nitrate synthesis. It is proposed that the pathway of nitrate biosynthesis may be the result of oxidation of reduced nitrogen compounds by oxygen radicals generated by an activated reticuloendothelial system.

Acetates↗
PubMed1984

Nitrosation by alkyl nitrites. Catalysis by inorganic salts.

Isobutyl nitrite is an effective nitrosating agent at acidic, neutral and basic pH in the presence of species arising from phosphate ion. The reaction is first-order in isobutyl nitrite and amine. In the reaction of isobutyl nitrite with sulfanilamide, the pH dependence reflects the change in concentration of the various protonated forms of phosphate, with H3PO4 and H2PO4- most strongly affecting the rate. In the reaction of isobutyl nitrite with dipropylamine, the pH dependence also reflects the change in the concentration of unprotonated amine.

Catalysis↗
PubMed1984

Monitoring exposure to 4-aminobiphenyl via blood protein adducts.

The feasibility of monitoring exposure to 4-aminobiphenyl (4-ABP) was determined by measuring the formation of covalent blood protein adducts in rats following administration of the amine. A single major adduct was obtained from serum albumin, which was formed from 4-acetylaminobiphenyl and the single tryptophan residue of albumin. The adduct was isolated as part of a tetrapeptide, following Pronase digestion and reverse-phase high-performance liquid chromatography purification, and was identified by amino acid analysis, 1H-nuclear magnetic resonance and mass spectrometry. This adduct was cleared in vivo and showed a half-life of 4.7 days, essentially identical to that of albumin. Similarly, 4-ABP yielded a single major adduct with haemoglobin. This adduct showed a stability in vivo that was comparable to that of haemoglobin, and was shown to accumulate, with chronic dosing, to a level 30 times higher than that resulting from a single dose. Treatment of adducted haemoglobin, with 0.1 N hydrochloric acid in acetone, caused hydrolysis and release of 4-ABP. The formation of the haemoglobin adduct involves 4-nitrosobiphenyl as an intermediate product and, by implication, 4-hydroxyaminobiphenyl. Thus, the haemoglobin adduct is a measure of the fraction of 4-ABP that is N-hydroxylated directly, whereas the albumin adduct reflects that portion which is acetylated prior to N-hydroxylation. Approximately 0.02% of a dose of 4-ABP was bound to the tryptophan in albumin (dose of 2-80 mg/kg) and 5% was bound to haemoglobin as an acid-labile adduct (dose of 0.5-5000 micrograms/kg).

Acetylation↗
PubMed1983

Mammalian nitrate biosynthesis: incorporation of 15NH3 into nitrate is enhanced by endotoxin treatment.

Incorporation of an oral dose of [15N]ammonium acetate into urinary [15N]nitrate has been demonstrated in the rat. Investigation of the regulation of nitrate synthesis has shown that Escherichia coli lipopolysaccharide potently stimulates urinary nitrate excretion (9-fold increase). It was further shown that the enhanced rate of nitrate excretion by lipopolysaccharide was due not to a reduction in nitrate metabolic loss but rather to an increased rate of synthesis. This conclusion was based on finding a proportionally increased incorporation of [15N]ammonium into nitrate nitrogen with lipopolysaccharide treatment. Nitrate biosynthesis was also increased by intraperitoneal injection of carrageenan and subcutaneous injection of turpentine. It is proposed that the pathway of nitrate biosynthesis may be the result of oxidation of reduced nitrogen compounds by oxygen radicals generated by an activated reticuloendothelial system.

Acetates↗
PubMed1983

Metabolic fate of an oral dose of 15N-labeled nitrate in humans: effect of diet supplementation with ascorbic acid.

The metabolic fate of a p.o. dose of 3.5 mmol 15N-labeled nitrate has been investigated in 12 healthy young adults. Samples of urine, saliva, plasma, and feces were collected over a period of 48 hr following administration of the dose. Subjects received either 60 mg of ascorbic acid, 2 g of ascorbic acid, or 2 g of sodium ascorbate per day. An average of 60% of the 15NO3- dose appeared in the urine as nitrate within 48 hr. Less than 0.1% appeared in the feces. The 15N label of nitrate was also found in the urine (3%) and feces (0.2%) in the form of ammonia or urea. The fate of the remaining 35% of the 15NO3- dose administered is unknown. No effect of ascorbic acid or sodium ascorbate on the nitrate and nitrite levels of plasma, saliva, urine, or feces was observed. A one-compartment pharmacokinetic model was used to describe the relationships between intake, plasma concentration, and urinary excretion of nitrate. The half-life of nitrate in the body was found to be approximately 5 hr, and its volume of distribution was about 30% of body weight. Daily endogenous biosynthesis of nitrate was estimated to be about 1 mmol/day.

Administration, Oral↗
PubMed1983

Pharmacokinetic model for N-nitrosodimethylamine based on Michaelis-Menten constants determined with the isolated perfused rat liver.

A pharmacokinetic model was constructed to describe the absorption, distribution, and metabolic clearance of N-nitrosodimethylamine. The model is composed of two compartments, total body water and the liver, which are linked by blood flow. Metabolic clearance is presumed to occur only in the liver. Liver clearance kinetics was determined with isolated perfused livers. Clearance appeared to obey Michaelis-Menten kinetics with Km = 8.3 +/- 4.8 microM and Vmax = 0.15 +/- 0.02 mumol/min . liver. The observed value for Km is about 1 order of magnitude lower than any observed when clearance is determined using liver microsome preparations. The model is used to calculate whole-body clearance of N-nitrosodimethylamine and relative tissue exposure as a function of the route of administration. The calculations are compared with previously published experimental data, and it is shown that the accuracy of the model for low doses is a result of the novel value observed for Km in the perfused liver.

Animals↗
PubMed1982

Formation of an activated N-nitroso compound in nitrite-treated fava beans (Vicia faba).

Fava beans are prominent in the diet of the Colombian population at high gastric cancer risk. Upon nitrite treatment under simulated gastric conditions, a potent mutagen was formed as detected by a forward mutation assay using Salmonella typhimurium TM677 without microsomal activation. The promutagen was partially purified by preparative t.l.c. and normal phase h.p.l.c. of the acetone-soluble portion of a dried aqueous extract. The nitrosated promutagen fully accounted for the mutagenicity observed with whole fava beans. One gram of fresh fava beans yielded approximately 0.35 nmol of mutagen. Mutagenicity data indicated that this mutagen was more potent than N-methyl-N'-nitro-N-nitrosoguanidine. The characteristics of the mutagen were typical of an activated N-nitroso compound, that is a compound in which the N-nitroso moiety is attached to an activating group, such as a carbonyl group. Irradiation of the mutagen yielded a Griess positive reaction. By reverse-phase h.p.l.c. photohydrolysis, a single peak could be ascribed to the mutagen. Its stability varied as a function of pH, being most unstable under alkaline conditions. Cysteine and phosphate concentration had no effect on its rate of decomposition, thereby strongly suggesting that the mutagen is an N-nitrosourea. The results obtained in this study support the hypothesis of carcinogenesis via the intragastric production of activated N-nitroso compounds.

Fabaceae↗
PubMed1982

In vivo stability of nitrite and nitrosamine formation in the dog stomach: effect of nitrite and amine concentration and of ascorbic acid.

Formation of N-nitrosodimethylamine (NDMA) from the precursors nitrate and dimethylamine has been studied in the chronically fistulated dog stomach. Measurements have also been made as a function of time for nitrite stability and gastric pH, and a nonabsorbable marker has been used to correct for gastric emptying and dilution. In the fasting animal NDMA forms within minutes after addition of the reactants if the pH is below 5. The presence of food in the stomach slows the reaction, and the additional presence of ascorbic acid greatly depresses the amount of NDMA formed. The concentration of nitrite in gastric juice declines rapidly after its introduction, but the concentration of NDMA declines even more rapidly than nitrite. This suggests that NDMA is probably rapidly absorbed directly from the dog stomach, in contrast to earlier results in rodent experiments.

Absorption↗
PubMed1982

Mutagenicity of N-nitroso bile acid conjugates in Salmonella typhimurium and diploid human lymphoblasts.

Two N-nitroso bile acid conjugates, N-nitrosotaurocholic acid and N-nitrosoglycocholic acid, were tested for mutagenicity by forward mutation assay in Salmonella typhimurium TM 677 and in diploid human lymphoblasts, line TK6. N-Nitrosoglycocholic acid and N-nitrosotaurocholic acid showed similar concentration-response curves in the bacterial assay with statistically significant mutant fractions observed at about 0.12 mM. Nonnitrosated parent compounds were nonmutagenic. However, in the human cell assay, N-nitrosotaurocholic acid gave statistically significant mutant fractions only at 0.4 mM, but N-nitrosoglycocholic acid was mutagenic at 0.05 microM, some 9000 times more potent. Experiments with quantitative Ames' S. typhimurium reversion assays indicated mutagenesis via base substitution.

Cell Line↗
PubMed1981

Nitrate synthesis in the germfree and conventional rat.

Metabolic balance studies show that germfree and conventional Sprague-Dawley rats synthesize nitrate. Equivalent results for germfree and conventional rats eliminate the microflora as obligatory components of nitrate production. Nitrate synthesis appears to be a mammalian process.

Animal Feed↗
PubMed1981

Nitrite stability and nitrosation potential in human gastric juice.

Human gastric juice samples were investigated from high- and low-risk areas (Colombia and Boston) for factors which influence the stability of nitrite and its potential for nitrosamine formation. The samples from individuals with chronic atrophic gastritis and intestinal metaplasia were not reactive to nitrite and supported a rate of nitrosation largely compatible with the nitrite and thiocyanate concentration. The samples from other individuals contained factors which destroyed nitrite and inhibited nitrosation. There were several samples from both groups which had an elevated rate of nitrosation catalyzed by unknown factors. It is suggested that continued hypochlorhydria might deplete gastric juice of its natural protective factors and lead to an elevated risk of gastric cancer in agreement with our earlier etiological model [1].

Colombia↗