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Biomedical subjects

R Preussmann

Publications and source records attributed to R Preussmann.

At least 37 records · Page 2Linked to original sources

Secondary amine precursors to nitrosamines in human saliva, gastric juice, blood, urine and faeces.

It has been suggested that the endogenous nitrosation of aliphatic, cyclic and heterocyclic secondary amines in the urinary bladder of patients with chronic urinary bacterial infections and in the human stomach may provide an important additional source of exposure to carcinogenic volatile N-nitrosamines. The most commonly occurring nitrosatable secondary amines found in human saliva, gastric juice, blood, urine and faeces are dimethylamine (DMA), pyrrolidine (PYR) and piperidine (PIP). All of 40 analysed samples of gastric juice contained 0.87 +/- 0.89 (SEM) microgram/ml DMA, 39 contained 1.35 +/- 2.53 microgram/ml PIP, 36 contained 0.18 +/- 0.15 microgram/ml PYR and 14 contained 0.05 +/- 0.11 microgram/ml diethylamine. Nitrate (14.0 +/- 15.7 microgram/ml) was present in all samples and 11 of 40 samples contained 0.43 +/- 1.38 microgram/ml nitrite. Only one gastric juice sample with pH less than 4.5 contained nitrite (0.1 microgram/ml). In paraplegics, patients with bladder augmentations and two control groups without bacterial infections of the urinary bladder, a mean daily excretion of 40.5-49.7 mg/day DMA, 19.4-23.8 mg/day PYR and 26.1-31.7 mg/day PIP was found. In both patient groups suffering from chronic bacterial infection of the urinary bladder, the corresponding volatile N-nitrosamines were formed by endogenous nitrosation and excreted in urine.

Bacteria↗

Increased exposure to dietary amines and nitrate in a population at high risk of oesophageal and gastric cancer in Kashmir (India).

Analytical data on aliphatic amines and nitrate from the most commonly used fresh and sun-dried vegetables, red chillies and a widely consumed beverage, salted tea, are presented from a high risk area for oesophageal and gastric cancer in Kashmir. Exposure estimates for the adult population show that high consumption of boiled Brassica vegetables leads to a high nitrate intake of 237 mg/day. The frequent consumption of hot salted tea is shown to result in exceptionally high exposure to methylamine (1200 micrograms/day), ethylamine (14,320 micrograms/day), dimethylamine (150 micrograms/day) and diethylamine (400 micrograms/day). The indiscriminate use of red chillies in the area leads to exposure to dimethylamine (280 micrograms/day), pyrrolidine (517 micrograms/day) and methylbenzylamine (40 micrograms/day). This is to our knowledge the first report where a chronic exposure to methylbenzylamine has been shown in a population at high risk of oesophageal cancer.

Adult↗

Potential of endogenous formation of volatile nitrosamines from Nigerian vegetables and spices.

Nitrosatability of dried Nigerian vegetables and spices was investigated under simulated gastric conditions. N-Nitroso-dimethylamine (NDMA) was the only volatile nitrosamine found above the preformed level except in ugwu where N-nitroso-piperidine (2.3 ppb) was also detected. The lowest NDMA value of 0.4 ppb was found in bitterleaf while onions had the highest level (14.7 ppb) of nitrosation. The results suggest that, under endogenous conditions, nitrosation of these foodstuffs could be an important contributory factor in cancer aetiology.

Food Preservation↗

Determination of primary and secondary amines in foodstuffs using gas chromatography and chemiluminescence detection with a modified thermal energy analyser.

A simple method is described for the determination of primary and secondary amines in foodstuffs by gas chromatography with a modified thermal energy analyser, operated in the nitrogen mode. Food samples were subjected to mineral oil vacuum distillation and the isolated amines were derivatized with benzenesulphonyl chloride to form the corresponding sulphonamides, which were fractionated to yield primary and secondary amine derivatives using a modified Hinsberg procedure. The detection limit for individual amines using a 10-g food sample was 10 micrograms/kg (ppb) and recoveries were in excess of 80%.

Amines↗

Volatile and nonvolatile nitrosamines in beer.

The occurrence of N-nitroso compounds was investigated at different stages in the production of four different beer types and in 14 retail beer samples. Only two N-nitroso compounds, namely N-nitrosodimethylamine (0.17 +/- 0.18 microgram/kg; not detected to 0.60 microgram/kg) and N-nitrosoproline (1.51 +/- 1.01 micrograms/kg; range 0.5-3.60 micrograms/kg) were detected. For moderate beer drinkers, the N-nitrosodimethylamine exposure levels are unlikely to present a significant health risk while the presence of noncarcinogenic N-nitrosoproline does not pose any hazard to human health.

Beer↗

Trace analysis of nitrosated foodstuffs for nitrosamides.

An analytical procedure previously developed for the trace determination of nitrosamides was applied to a screening of nitrosated foodstuffs for nitrosoureas. Different types of foodstuffs were nitrosated both under chemical conditions using a high nitrite concentration, and under simulated gastric conditions. Methylating activity corresponding to N-nitroso-N-methylurea (MNU) was detected in most samples. Under chemical conditions, the yields spanned several orders of magnitude with processed fish and meat products being at the top, and plant products at the bottom of the scale. After nitrosation under simulated gastric conditions, the range of MNU activity was significantly smaller. No correlation exists between the yields determined under chemical and simulated gastric conditions.

Animals↗

Tobacco-specific N-nitrosamines in tobacco and mainstream smoke of Indian cigarettes.

Different brands of Indian cigarettes were analysed, by gas chromatography-thermal energy analysis, for the presence of carcinogenic tobacco-specific N-nitrosamines (TSNA) in both tobacco and mainstream smoke. Preformed TSNA in cigarette tobacco ranged between 68 and 730 ng N-nitrosonornicotine (NNN)/cigarette, between 19 and 174 ng 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK)/cigarette and between 98 and 519 ng N-nitrosoanabasine (NAB) together with N-nitrosoanatabine (NAT)/cigarette. The amounts of NNN, NNK and NAB/NAT in mainstream smoke were 11-156, 7-73 and 17-146 ng/cigarette, respectively.

Chromatography, Gas↗

Mean daily intake of volatile N-nitrosamines from foods and beverages in West Germany in 1989-1990.

The levels of volatile N-nitrosamines were determined in 38 alcoholic drinks and 215 food samples prepared for human consumption using standard culinary practices. The analyses used gas chromatography-thermal energy analysis. Detectable levels were found in 80 (31.5%) of the individual samples. The average daily intake of volatile N-nitrosamines in West Germany in 1989-1990 was found to be: 0.28 microgram N-nitrosodimethylamine (NDMA)/day, 0.011 microgram N-nitrosopyrrolidine (NPYR)/day and 0.015 microgram N-nitrosopiperidine (NPIP)/day for men, and 0.17 microgram NDMA/day, 0.011 microgram NPYR/day and 0.015 microgram/NPIP/day for women. For men, 31% of the daily NDMA exposure results from the consumption of beer.

Adult↗

Mean daily intake of primary and secondary amines from foods and beverages in West Germany in 1989-1990.

264 samples of foods and beverages from the German market in 1989-1990 were analysed for primary and secondary amines. Amines were determined as benzenesulphonyl chloride derivatives by gas chromatography with chemiluminescense detection. The mean daily intake of primary amines was calculated to be 29 mg/day for women and 37 mg/day for men. For secondary amines, the mean daily intake was 6 mg/day for women and 8 mg/day for men.

Adult↗

Comparative metabolism and urinary excretion of N-mononitrosopiperazine and N,N'-dinitrosopiperazine in the rat.

The metabolism of N-mononitrosopiperazine (NPz) and N,N'-dinitrosopiperazine (DNPz) was investigated in Sprague-Dawley rats. When an oral dose of 50 micrograms/rat NPz was administered, 10.5% of the dose was recovered unchanged in urine together with N-nitroso-3-hydroxypyrrolidine (NHPYR, 1.3% of administered NPz dose) and N-nitrosodiethanolamine (NDELA, 0.3%). For DNPz, 7.7% of the administered dose together with NPz (0.04%), NHPYR (2.9%), NDELA (6.7%) and N-nitroso(2-hydroxyethyl)glycine (NHEG, 20.2%) was recovered in urine after 24 h. These results show extensive metabolism of both NPz and DNPz and suggest that both NPz and NHPYR could be analysed in urine as markers for the endogenous nitrosation of piperazine in patients receiving antihelminthic treatment with piperazine.

Animals↗

N-nitroso compounds in cigarette tobacco and their occurrence in mainstream tobacco smoke.

The tobacco and mainstream smoke of 20 commercial brands of filter and non-filter cigarettes were analysed for N-nitroso compounds. The concentrations of N-nitrosodimethylamine (NDMA), N-nitrosoethylmethylamine (NEMA) and N-nitrosopyrrolidine (NPYR) in cigarette tobacco were very much lower than in mainstream smoke, where the levels were 6.3-76.4 ng/cig NDMA, less than 1.0-7.1 ng/cig NEMA and 3.9-41.2 ng/cig NPYR. N-Nitrosodiethylamine was not detected in mainstream smoke and N-nitrosopiperidine (less than 1.0 ng/cig) was detected in the smoke of four unfiltered cigarette brands. The five major non-volatile nitrosamines present in cigarette tobacco were 4-(N-nitroso-N-methylamino)butyric acid (not detected to 200 ng/cig), N-nitrosopipecolic acid (not detected to 670 ng/cig), N-nitrososarcosine (22-460 ng/cig), 3-(N-nitroso-N-methylamino)propionic acid (110-4990 ng/cig) and N-nitrosoproline (580-15000 ng/cig). The tobacco-specific nitrosamines N-nitrosoanabasine and N-nitrosoanatabine were found at levels of 270-2330 ng/cig and 18-205 ng/cig in cigarette tobacco and mainstream smoke respectively. N-Nitrosonornicotine was present at 400-5340 ng/cig and 19-855 ng/cig in cigarette tobacco and mainstream smoke respectively. 4-(N-Nitrosomethyl-amino)-1-(3-pyridyl)-1-butanone concentrations of 100-960 ng/cig and 21-470 ng/cig in cigarette tobacco and mainstream smoke were determined. 4-(N-Nitrosomethyl-amino)-4-(3-pyridyl)-1-butanol (iso-NNAL) was detected in four dark (French) tobacco unfiltered cigarettes at a concentration range of 140-240 ng/cig and 5-11 ng/cig in the corresponding mainstream smoke. For non-filter cigarettes, a transfer rate of 3.4-4.6% for iso-NNAL was calculated.

Germany, West↗

Increased urinary nitrosamine excretion in paraplegic patients.

An increased risk of bladder cancer is a recognized complication in spine-injured patients undergoing long-term urethral catheterization to preserve renal function. Aerobic cultures from 28 of 30 paraplegic patients showed complex bacterial flora containing nitrate-reducing organisms (Escherichia coli, Proteus and Klebsiella spp.). Urine samples from 29 paraplegic patients were also found to contain volatile nitrosamines. Mean N-nitrosamine excretion levels were 0.65 +/- 0.69 micrograms/day N-nitrosodimethylamine, 0.25 +/- 0.44 micrograms/day N-nitrosopiperidine and 0.39 +/- 0.50 micrograms/day N-nitrosopyrrolidine. A mean urinary nitrite excretion of 10.4 +/- 13.2 mg/day was found in 24 out of 30 paraplegic patients. In the sterile urine of control volunteers (medical staff attending the paraplegic patients and in-patients from other wards of the hospital), no urinary excretion of volatile N-nitrosamines and nitrite was found. The results clearly demonstrate a bacterially mediated in vivo formation of N-nitroso compounds in the urinary tracts of paraplegic patients which may be an important etiological risk factor for bladder cancer in this patient group.

Amines↗

Endogenous formation of N-nitrosamines from piperazine and their urinary excretion following antihelmintic treatment with piperazine citrate.

Antihelmintic treatment with piperazine (1,4-diazacyclohexane) for microfilarie parasitism results in the endogenous formation of piperazine-derived N-nitrosamines. The urinary excretion of these N-nitrosamines was determined by biochemical monitoring of 14 patients receiving 2 g piperazine citrate. The urinary excretion (mean +/- SD) of N-mononitrosopiperazine (MNPz) was 27.0 +/- 26.7 micrograms/day (range 0.6-96.0 micrograms/day). Trace levels of 0.73 +/- 0.92 micrograms/day N,N'-dinitrosopiperazine (DNPz) (range ND-2.8 micrograms/day) were also found in 7 of 14 urine samples. N-Nitroso-3-hydroxypyrrolidine (NHPYR), a metabolite of both MNPz and DNPz, was detected in 11 of 14 urine samples at a mean concentration of 1.74 +/- 1.72 micrograms/day (range ND-5.7 micrograms/day) and traces of N-nitrosodiethanolamine in two samples at levels of 0.3 and less than 0.1 micrograms/day. The results show that biochemical monitoring of urinary NHPYR may be a good indicator of endogenous MNPz formation. While DNPz was also detected in urine, conclusive validation for its endogenous formation could not be provided because no evidence was found for the presence of its major metabolite, N-nitroso-(2-hydroxyethyl)glycine in urine.

Adult↗

Urinary nitrate, nitrite and N-nitroso compounds in bladder cancer patients with schistosomiasis (bilharzia).

Urinary excretion of nitrite and of volatile and nonvolatile N-nitroso compounds is increased in schistosomiasis (bilharzia) patients with Schistosoma haematobium infection. This observation suggests that the formation of nitrite and N-nitroso compounds in vivo in the urinary bladder of bilharzial patients may be an important etiological factor in the induction of bladder cancer associated with S. haematobium infection.

Adult↗

Dietary sources of N-nitrosamines in a high-risk area for oesophageal cancer--Kashmir, India.

Samples of foods consumed frequently in Kashmir, a high-risk area for oesophageal cancer, were analysed for the presence of volatile N-nitrosamines. Relatively high levels of N-nitrosodimethylamine (NDMA), N-nitrosopiperidine (NPIP) and N-nitrosopyrrolidine (NPYR) were detected in smoked fish (20 micrograms/kg NDMA), sun-dried spinach (5.8 micrograms/kg NDMA; 23.8 micrograms/kg NPIP), sun-dried pumpkin (24.6 micrograms/kg NPYR) and dried, mixed vegetables (10 micrograms/kg NDMA). The possible role of N-nitrosamines in the etiology of oesophageal cancer in Kashmir is discussed.

Diet↗

Trace analysis of N-nitrosoureas by their alkylating activity.

N-Nitrosoureas can be analysed indirectly by gas chromatography with chemoluminescence detection after reaction of the corresponding diazoalkanes with the scavenger reagent N-nitroso-N-tert-butylglycine. A lower determination limit of 2 ng N-methyl-N-nitrosourea per sample is achieved. The method is specific for N-nitroso compounds, which release nonpolar diazoalkanes upon alkaline treatment.

Alkylation↗

Tobacco-specific nitrosamines in commercial cigarettes: possibilities for reducing exposure.

Tobacco-specific nitrosamines (TSNA) are powerful carcinogens found in tobacco and tobacco smoke in relatively high concentrations. Tar delivery, which is generally accepted as an index for the carcinogenic potential of cigarette smoke, must be declared in most European countries. In this investigation of more than 170 types of commercial cigarettes from several European countries and the USA, no correlation was observed between tar delivery and mainstream smoke concentration of N'-nitrosonornicotine (NNN) and 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK). Therefore, although crucial, tar delivery alone is not a sufficient index for the carcinogenic potential of cigarette smoke. It is proposed that TSNA concentrations be determined for characterization of the carcinogenic potential of cigarettes with low and ultra-low tar yields and that these be declared by an additional and adequate parameter. The mainstream smoke concentrations of NNN and NNK are given by the amounts of preformed compounds in tobacco, which is dependent on the nitrate content of the tobacco and the tobacco type. A further important determinant of the exposure of smokers to TSNA is the total volume drawn through a cigarette while smoking, which is dependent on puff volume and puff frequency and which directly influences TSNA transfer. Smokers inhale higher volumes when smoking low-nicotine cigarettes, so that low NNN:nicotine and NNK:nicotine ratios result in decreased exposure to TSNA. Reduction of exposure to TSNA can be achieved by selecting tobaccos with low levels of preformed TSNA (low nitrate content, small amounts of burley tobaccos and stems) and by manufacturing cigarettes with low NNN:nicotine and NNK:nicotine ratios.

Carcinogens↗

Occurrence of and exposure to N-nitroso compounds in tobacco.

The concentrations of 21 N-nitroso compounds in smokeless tobaccos are presented. Tobacco-specific nitrosamines accounted for 70-90% of the total identified N-nitroso compounds. Daily exposure of smokeless tobacco users to preformed N-nitroso compounds may exceed 200 micrograms/day in certain populations.

Humans↗