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Biomedical subjects

A R Tricker

Publications and source records attributed to A R Tricker.

At least 37 records · Page 2Linked to original sources

N-nitrosamine generation by urinary tract infections in spine injured patients.

Urine was collected from 33 patients resident at the Welsh Spinal Injuries Unit and analysed for volatile N-nitrosamines by gas chromatography. N-nitrosodime-thylamine, N-nitrosopiperidine or N-nitrosopyrrolidine was detected in 32 of the samples. Thirty-one of the samples were infected by one or more microbial species. Nitrate and N-nitrosamines were not found in the sterile urines of a group of 10 control individuals exposed to the same dietary and environmental influences as the spinal patients. Although N-nitrosamines were found in some of the catheter drainage system products, they did not elute into urine on 24-h exposure. In addition, 6 of the nitrosamine-containing urines had no contact with drainage systems as they were collected from spinal patients who were capable of independent voiding. It was concluded that the nitrosamines detected in the urines arose from the bacterial nitrosation of urinary amines. These results support the hypothesis that chronic urinary tract infection may have a role in the aetiology of bladder cancer in spine injured patients.

Humans↗

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↗

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↗

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↗

Tumor induction in a rat model for ureterosigmoidostomy without evidence of nitrosamine formation.

Twenty rats were randomized into a vesicosigmoidostomy and an unoperated control group. In both groups the 24 hour excretion of secondary amines, nitrate, nitrite and nitrosamines was measured before and after gavage of proline and nitrate, piperazine and nitrate, N-nitrosoproline, mono-N-nitrosopiperazine. The urinary nitrosamine concentrations were not significantly different between both groups neither before nor after application of the several substances. Thirty rats were randomized into two vesicosigmoidostomy groups with and without antibiotic coverage and an unoperated control group. After ligation of distal rectum and mesosigmoid the rectosigmoids were removed. No significant concentrations of volatile nitrosamines could be measured in the rectosigmoid contents of the three groups. One hundred and twenty rats randomized into three groups following vesicosigmoidostomy received the potential nitrosamine antidotes sodium-2-mercaptoethane sulfonate or sodiumpentosan-polysulfate or acted as controls. 12/118 (10.2%) developed adenomas and 25/118 (21.2%) adenocarcinomas at the vesico-colonic anastomosis with no significant differences between the three groups concerning tumor incidence or mortality. The results show that colon carcinomas occur in a rat model for ureterosigmoidostomy without evidence for thus induced nitrosamine formation. This and the missing effect of nitrosamine antidotes suggest that other factors than nitrosation must be responsible for colon carcinogenesis following urinary diversion via intestine.

Adenocarcinoma↗

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↗

Effect of vitamin C on endogenous formation of N-nitrosamines in ureterosigmoidostomy patients.

The bacterially catalyzed formation of nitrosamines in the rectosigmoid is a favorite theroy for the increased risk of colon carcinomas following ureterosigmoidostomy. The urine/feces mixtures of 20 ureterosigmoidostomy patients were analyzed for nitrate, nitrite, volatile and nonvolatile nitrosamines prior to, and after, oral administration of vitamin C, a known nitrosation inhibitor. Following a 4-week period of daily ingestion of 2 g vitamin C (1 g in children) there was a slight, but not significant, decrease of volatile and nonvolatile nitrosamines and nitrite, as well as a nonsignificant increase in nitrate in the urine/feces of these patients. No correlation between the vitamin C concentration in serum or urine/feces mixture and the nitrosamine excretion was observed. These results suggest that the administration of vitamin C is not a suitable method for prophylaxis of endogenous nitrosation in ureterosigmoidostomy patients. Clinical and experimental findings implicate that factors other than nitrosamines play an important role in colon carcinogenesis of patients with ureterosigmoidostomies or other forms of urinary diversions using the small or large bowel.

Ascorbic Acid↗

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↗

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↗

N-nitroso compounds and their precursors in Brassica oleracea.

In the present study, Brassica a dried green vegetable from Kashmir, which is a major constituent of the local diet, was analysed for nitrosatable aliphatic amines, N-nitrosamines prior to and after nitrosation) and alkylating activity due to N-nitrosamides following nitrosation. The cooked vegetable contained 11 micrograms/kg nitrosodimethylamine and 21 micrograms/kg nitrosopyrrolidine. Nitrosation under chemical conditions yielded 1200 micrograms/kg N-methylnitrosourea.

Brassica↗

The role of nitrate, nitrite and N-nitrosamines in carcinogenesis of colon tumours following ureterosigmoidostomy.

Urinary diversion in both a rat model for ureterosigmoidostomy and in ureterosigmoidostomy patients result in an increased incidence of colon tumours. Bacterial and chemical investigations on feces-urine mixtures from both the rat model and ureterosigmoidostomy patients showed the presence of a complex nitrate-reducing bacterial flora in both rats and humans. This bacterial flora actively reduced urinary nitrate to nitrite in humans and increased the endogenous formation of N-nitroso compounds. No evidence of urinary nitrate reduction and increased nitrosamine formation in the rectosigmoid of rats was found. The results support the N-nitrosamine theory of carcinogenesis of the colon following ureterosigmoidostomy in humans, but not in rats. As the rat model induces colon carcinomas, factors other than the increased endogenous formation of N-nitroso compounds in the rectosigmoid may contribute to the initiation of colon carcinomas following ureterosigmoidostomy.

Animals↗