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Biomedical subjects

R Preussmann

Publications and source records attributed to R Preussmann.

At least 73 records · Page 4Linked to original sources
PubMed1989

Proline is not useful as a chemical probe to measure nitrosation in the gastrointestinal tract of patients with gastric disorders characterised by anacidic conditions.

Aspirated fasting gastric juice from patients with lesions of the gastrointestinal tract and from healthy controls was analysed for nitrite before and after (30, 90, and 240 min) oral administration of 200 mg nitrate. Wilcoxon's rank-sum tests showed no significant differences in fasting gastric juice nitrite concentrations between healthy controls and patients after proximal gastral vagotomy or with gastric/duodenal ulcer (median less than or equal to 0.7 ppm NO-2) and only moderate increases after nitrate administration. Chronic atrophic gastritis patients and patients with Billroth I or II gastric resections showed median concentrations of 2 ppm NO-2 which increased to 20 ppm (up to 200 ppm in one Billroth II patient) after administration of nitrate. Endogenous formation of N-nitrosoproline using the NPRO-test was determined in two groups with low (healthy control and proximal gastral vagotomy patients) and high (Billroth I and II patients) gastric nitrite concentrations. After 12 h fasting, 200 mg nitrate was orally administered, followed 30 min later by 500 mg L-proline. Endogenously formed N-nitrosoproline which is quantitatively excreted in urine was determined in urine over the following 24 hours. In over 80% of the urine samples collected from Billroth I and II patients no detectable NPRO was found whilst in over 85% of the healthy controls and proximal gastral vagotomy patients up to 33.5 micrograms NPRO was detected. In vitro nitrosation kinetics showed that at gastric pH greater than 4 present in both, patients with Billroth I and II resections and with chronic atrophic gastritis, nitrosation of proline does not occur. As alternative chemical probes for quantifying potential endogenous nitrosation in hypoacidic patients the methyl and ethyl esters of proline were investigated. In vivo nitrosation of these two new probes was established in animal experiments using rats and was shown to occur in vitro at pH 4-5. During incubation in human gastric juice, however, almost 30% ester cleavage by non-specific gastric esterases occurred within the first five minutes, thus further limiting the use of these compounds in determining endogenous nitrosation in hypoacidic patients.

Gastric Acidity Determination↗
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

Quantitative morphometric comparison between the expression of two different "marker enzymes" in preneoplastic liver lesions induced in rats with low doses of N-nitrosodiethanolamine.

Male Sprague-Dawley rats were treated with low doses of N-nitrosodiethanolamine (NDELA) (0.2, 0.63, 1.5, 6 and 25 mg/kg body wt per day). Foci of altered hepatocytes developed at all dose levels. The extent of foci positive for gamma-glutamyl transpeptidase (gamma-GT), as demonstrated histochemically in frozen sections, was quantitated morphometrically and compared with the data obtained earlier in the same livers by measuring the extent of foci positive for glucose-6-phosphate dehydrogenase (G6PDH). The area density of foci positive for gamma-GT was much smaller than that of foci positive for G6PDH at all dose levels and time points studied. However, there was an increase in the area density of both gamma-GT- and G6PDH-positive foci proportionally to the time of treatment and the total dose of the carcinogen administered. The dose-time relation for the induction of 0.5% gamma-GT positive liver tissue assessed as a double logarithmic plot gives a straight line. The same holds true for the induction of 1% G6PDH-positive liver tissue. The slopes of these straight lines are identical, and they have the same characteristics as the line indicating the time when 50% of the animals developed liver tumors at higher doses. Thus, a close statistical correlation of enzyme altered hepatic foci and the development of hepatocellular tumor exists irrespective of the absolute amount of the area density of the respective foci.

Animals↗
PubMed1988

The occurrence of tobacco-specific nitrosamines in oral tobacco products and their potential formation under simulated gastric conditions.

The levels of the tobacco-specific nitrosamines: N-nitrosoanabasine, N-nitrosoanatabine, N-nitrosonornicotine and 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone in a variety of chewing tobaccos, oral snuffs, masheri and zarda samples were determined. The potential endogenous formation of tobacco-specific nitrosamines was estimated by incubation of tobacco samples at pH 2.0 for 1 hr at 37 degrees C and over the pH range 1.0 to 5.5 under conditions simulating the normal fasting stomach, with a constant nitrite concentration of 25 microM. Under the simulated gastric conditions, N-nitrosoanabasine, N-nitrosoanatabine and N-nitrosonornicotine were formed, and maximum formation of these tobacco-specific nitrosamines occurred at pH 2.5. Nicotine, the major alkaloid present in tobacco and precursor to N-nitrosonornicotine and 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone, was not nitrosated. The formation of N-nitrosonornicotine resulted from nitrosation of nornicotine, another alkaloid also present in tobacco. Under the acidic simulated gastric conditions, slight decomposition of 4-(N-nitrosomethyl-amino)-1-(3-pyridyl)-1-butanone via transnitrosation was observed.

Carcinogens↗
PubMed1988

Occurrence of volatile N-nitrosamines in dried chillies.

Twenty samples of dried chillies, fresh chillies and chilli sauces have been analysed for the presence of volatile N-nitrosamines. Over 75% of both dried whole chillies and chilli powder samples analysed contained N-nitrosodimethylamine and N-nitrosopyrrolidine (NPYR) at concentrations of 0.66-16.5 micrograms/kg and 0.48-6.0 micrograms/kg, respectively. Fresh chillies and chilli sauces were not found to contain volatile N-nitrosamines.

Condiments↗
PubMed1988

The occurrence of preformed N-nitroso compounds in food samples from a high risk area of esophageal cancer in Kashmir, India.

Several commonly used raw foodstuffs from a high risk esophageal cancer region in Kashmir (India) were analysed for the presence of N-nitroso compounds. The food items were selected on the basis of their frequent consumption with particular emphasis on the preserved foods (dried, pickled and smoked) and those which are unique to the region. Nine out of 11 food items were found to contain low concentrations of N-nitrosodimethylamine (NDMA), N-nitrosopyrrolidine (NPYR), N-nitrososarcosine (NSAR), N-nitrosoproline (NPRO) and N-nitrosothaizolidine-4-carboxylic acid (NTCA). The preliminary survey shows a widespread contamination of N-nitroso compounds in raw foodstuffs from Kashmir.

Esophageal Neoplasms↗
PubMed1988

Formation of N-nitroso compounds under simulated gastric conditions from Kashmir foodstuffs.

Several foodstuffs and teas from an area of high esophageal cancer risk in Kashmir (India) were studied under simulated gastric conditions with a realistic nitrite concentration for the formation of N-nitroso compounds. N-Nitrosodimethylamine (NDMA), N-nitrosoproline (NPRO), N-nitrosothiazolidine-4-carboxylic acid (NTCA) and N-nitrosopipecolic acid (NPIC) were the main products in different foods. Significant amounts of NDMA were formed from dried fish (20 micrograms/kg), dried and pickled vegetables (35.6 micrograms/kg and 7.3 micrograms/kg), locally grown Brassica oleracea ('Hak') leaves (69.9 micrograms/kg), and the traditional tea 'Kehwa' (9.2 micrograms/kg). The highest level of NTCA was formed in smoked fish (3294 micrograms/kg). 'Salted tea' prepared according to local method formed considerable amounts of NPRO (360 micrograms/kg) and NPIC (5870 micrograms/kg) along with 3 yet unidentified non-volatile N-nitroso compounds. High values of 4315 micrograms/kg NPIC were also obtained following nitrosation of red chillies and mixed spice cake ('Wur') under simulated gastric conditions. These results suggest the possibility of an appreciable endogenous formation of N-nitroso compounds from local foods in Kashmir.

Food↗
PubMed1988

Dose-time relationship of the development of preneoplastic liver lesions induced in rats with low doses of N-nitrosodiethanolamine.

The carcinogenic efficiency of very low doses of N-nitrosodiethanolamine (NDELA), an N-nitroso compound of environmental significance, was assessed by administering it to male Sprague-Dawley rats at five different dose levels: 0.2, 0.63, 1.5, 6 and 25 mg/kg b.w./day in the drinking water. Quantitation of the numbers and size of liver foci positive for glucose-6-phosphate dehydrogenase (G6PDH) by morphometric methods revealed a good correlation between the dose and duration of carcinogen treatment and the extent of G6PDH-positive foci development. Thus the area density increased proportional to time and dose. The dose-time relation for the induction of 1% G6PDH-positive liver tissues assessed as a double logarithmic plot gives a straight line with the same characteristics as that which results when the induction of liver tumors is evaluated.

Animals↗
PubMed1988

The initiator tRNA acceptance assay as a short-term test for carcinogens. 2. Results with ten compounds selected by the International Programme on Chemical Safety for the evaluation of short-term tests for carcinogens.

Eight carcinogenic and two non-carcinogenic compounds that are difficult to detect by short-term tests (acrylonitrile, benzene, benzoin, caprolactam, diethylhexylphtalate, diethylstilbestrol, hexamethylphosphoramide, phenobarbital, safrole and o-toluidine) were tested independently in Prague and in Heidelberg by the newly developed initiator tRNA acceptance assay. Seven out of eight tested carcinogens gave a positive response in this assay, only safrole showed a false negativity in both laboratories. Both non-carcinogenic compounds, benzoin and caprolactam, exhibited no activity. An absolute qualitative agreement was found with all compounds tested between the results of both laboratories. With the exception only of phenobarbital (intermediate activity in Prague and low in Heidelberg) the quantitative results obtained in both laboratories were comparable. The initiator tRNA acceptance assay thus appears to be a reliable short-term test for carcinogenicity with good reproducibility.

Carcinogens↗
PubMed1988

The initiator tRNA acceptance assay as a short-term test for carcinogens. 3. Results with 69 N-nitroso compounds.

The activity of 69 carcinogenic and non-carcinogenic N-nitroso compounds was tested by the recently developed initiator tRNA acceptance assay for carcinogens. Of 51 carcinogens tested, 50 were active in the assay. Only N-nitrosopropylpropanolamine showed a false negativity. Eleven out of 14 tested non-carcinogenic compounds were not active in the assay, nitrosoethyl-tert-butylamine and nitrosoprolineethylester were positive. As calculated from these data, the sensitivity of the assay was 98.0%, specificity 84.6%, accuracy 95.4% and predictive value 94.4%. Comparison of relative carcinogenicities in animal bioassays with quantitative results (% stimulation of initiator tRNA charging) of the short-term test showed a good correlation for non-carcinogenic compounds and strong carcinogens. However, carcinogens of low and median potency could not be easily distinguished. A good correlation was obtained for three isomer N-nitrosomethylaminopyridines between the TD50-value and activity in the tRNA acceptance assay. The initiator tRNA acceptance assay thus seems preferable for recognizing and classifying carcinogenic and non-carcinogenic N-nitroso compounds than any other individual short-term test for carcinogenicity.

Animals↗
PubMed1987

Nitrosation products from the plant Ephedra altissima and their potential endogenous formation.

The plant species Ephedra is commonly used in both folk medicine and for the preparation of health teas. Nitrosation of a tea made from Ephedra altissima yielded N-nitrosoephedrine (NEP), N-nitrosopseudoephedrine (NPEP), N-nitrosoproline (NPRO), N-nitrosomethylbenzylamine (NMBA), trace quantities of 2 unidentified non-volatile nitrosamines and the new nitroso compound 2-(N-nitroso-N-methylamino)propiophenone (NMAP). Incubation of a tea extract at 37 degrees C and pH 2.0 under conditions simulating the normal fasting stomach with a constant nitrite concentration (25 microM) for 1 h produced NEP, NPEP, NMAP and NPRO. The synthesis and preliminary results for the mutagenic effect of NMAP on the reversion of Salmonella typhimurium strains TA100 and TA1535 in the Ames test are reported.

Dimethylnitrosamine↗
PubMed1987

Influence of cysteine and nitrate on the endogenous formation of N-nitrosamino acids.

The excretion of N-nitrosamino acids and nitrate in 24-h urine was studied over a continuous 45-day period for a single volunteer on a supplemented diet regime. Days 1-10 (normal diet), 11-20 (normal diet + 600 mg nitrate/day), 21-25 (normal diet), 26-30 (normal diet + 200 mg L-cysteine/day), 31-35 (normal diet), 36-40 (normal diet + 600 mg nitrate + 200 mg L-cysteine/day) and days 41-45 (normal diet). The presence of N-nitrosohydroxyproline (NHPRO) in human urine is reported for the first time as well as the influence of L-cysteine on the formation of N-nitrosothiazolidine-4-carboxylic acid (NTCA) and N-nitroso-2-methylthiazolidine-4-carboxylic acid (NMTCA) under a normal nitrate burden (75 mg/day) and a high nitrate burden (675 mg/day). After estimation of the amount of dietary nitrite consumed and the extent of nitrite formation by bacterial reduction of nitrate in the oral cavity, the total daily exposure to nitrite was calculated. From a total daily exposure of 7.2 mg nitrite/day from a typical European diet, 0.08% is required for the endogenous formation of N-nitrosamino acids found in urine. Under an increased nitrate burden (675 mg/day), the total exposure to nitrite was increased to 38 mg/day of which 0.14% was required for the endogenous formation on N-nitrosamino acids.

Adult↗
PubMed1987

2-(N-nitroso-N-methylamino)propiophenone, a direct acting bacterial mutagen found in nitrosated Ephedra altissima tea.

A new N-nitroso compound identified in a nitrosated tea extract made from the plant Ephedra altissima and shown to be formed under in vivo conditions was identified as 2-(N-nitroso-N-methylamino)propiophenone (NMAP). N-Nitrosoephedrine (NEP), another N-nitroso compound detected in nitrosated Ephedra altissima tea and NMAP are shown to exert mutagenic activity in the Salmonella/mammalian microsome mutagenicity (Ames) test. Base-pair substitution mutation-detecting strains (TA100 and TA1535) showed both compounds to be weak direct-acting mutagens without the addition of S9-mix. The identification, synthesis and mutagenicity of NMAP are discussed.

Mutagenicity Tests↗
PubMed1987

Analysis of N-nitrosamines for genotoxicity in primary hepatocytes derived from various species.

DNA single-strand breaks (SSB) were induced in metabolically competent primary hepatocytes from rats, hamsters and pigs by a series of N-nitrosamines with organ-specific activities. Both hepatotrophic and nonhepatotropic carcinogens were genotoxic in the liver cells of all three species. Nonhepatotropic compounds were active at relatively lower doses than liver carcinogens in all species tested, substantiating many previous findings that organ-specific activation is not the primary determining factor of organ susceptibility to cancer. In 11 experiments of almost identical quality, the degree of SSB induced by 6.25 mumol N-nitrosodimethylamine varied by 75%. This high interindividual variability, even among hepatocytes derived from a single rat strain, indicates that the slight differences seen between rat, hamster and pig hepatocytes are not necessarily due to differences in species susceptibility.

Animals↗
PubMed1987

Formation of N-nitrosoiminodialkanoic acids and their unsuitability as biological monitors for endogenous nitrosation of dipeptides.

Nitrosation of dipeptides that do not contain imino amino acids leads to rearrangement and formation of N-nitrosoiminodialkanoic acids. The optimal pH is 2.0 (0.8-3.2% yield). Under normal gastric conditions, a maximum yield of 0.1 mumol total N-nitrosoiminodialkanoic acid would be obtained for a typical dietary intake of 0.1 mol dipeptide. This corresponds to a total concentration of about 20 micrograms N-nitrosoiminodialkanoic acid/l gastric juice over a 24-h period. N-Nitrosoiminodialkanoic acids are excreted quantitatively in urine when fed by gavage to rats; however, they were not detected in normal human urine. It was concluded that determination of these compounds in human urine is not a suitable method for monitoring endogenous nitrosation of dipeptides.

Animals↗
PubMed1987

Prevention of exposure to N-nitrosamines in the rubber industry: new vulcanization accelerators based on 'safe' amines.

Introduction of 'safe' amino components into traditional accelerator molecules could be an effective measure to prevent formation of carcinogenic N-nitroso compounds during rubber production. About 20 new derivatives of the dithiocarbamate and sulfenamide class, based on 'safe' amines, were synthesized and shown to be suitable for industrial application. Some of the corresponding N-nitrosamines were prepared and investigated for mutagenicity in Salmonella typhimurium TA1535. No or weak mutagenic potential was observed in most cases. The nitrosatability of five sulfenamides derived from 'safe' amines was determined and found to be substantially lower than that of a commercial sulfenamide accelerator tested under identical conditions.

Animals↗