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Biomedical subjects

B Spiegelhalder

Publications and source records attributed to B Spiegelhalder.

At least 55 records · Page 3Linked to original sources
PubMed1994

Nitrate, nitrite and volatile N-nitroso compounds in the urine of Schistosoma haematobium and Schistosoma mansoni infected patients.

The present study presents, for the first time, the amounts of nitrate, nitrite and volatile N-nitroso compounds in saliva and urine samples of Schistosoma haematobium and Schistosoma mansoni infected patients. Mid-morning saliva and 24 h urine samples were collected from male patients infected with S.haematobium (n = 129 saliva and 79 urine samples) and S.mansoni (n = 64 saliva and 65 urine samples) and in a comparative control group of healthy individuals (n = 27) from the Nile Delta region of Egypt. Saliva samples were analyzed for the presence of nitrate and nitrite; while urine samples were analyzed for the presence of nitrate, nitrite and volatile N-nitroso compounds. In the control group, N-nitroso-dimethylamine (NDMA) was detected at concentrations (mean +/- SD) of 0.27 +/- 0.47 microgram/day. N-Nitrosopiperidine (NPIP; 0.6 microgram/day) and N-nitrosopyrrolidine (NPYR; 0.4 microgram/day) were also present in one sample. S.mansoni infected subjects showed significantly (P < 0.001) higher levels of 2.9 +/- 2.9 micrograms/day NDMA and a higher frequency of NPIP (in 40/65 samples; 0.4 +/- 0.3 microgram/day) and NPYR occurrence (in 59/65 samples; 0.9 +/- 0.9 microgram/day). Significant further increases in the excretion of volatile N-nitroso compounds were found in S.haematobium-infected patients with mean daily excretion of 19.2 +/- 21 micrograms/day NDMA (in all samples; P < 0.001), 1.6 +/- 2.3 micrograms/day NPIP (in 56/79 samples; P < 0.001) and 1.3 +/- 1.9 micrograms/day NPYR (in 58/79 samples; P < 0.1). The differences either in salivary nitrite/nitrate or in urinary nitrite between the three distinct groups were not significant. However, the urinary excretion of nitrate was elevated from 139 +/- 82 mg/day in the control group to 249 +/- 126 mg/day in S.mansoni infected patients (P < 0.001) and to 174 +/- 176 mg/day in S.haematobium infected subjects (P < 0.005 in comparison to S.mansoni infected group). These results suggest a possible role of N-nitroso compounds in the etiology of schistosome-associated bladder cancer and imply a partial participation of S.mansoni in the multistage process of urinary schistosomiasis-associated bladder carcinogenesis.

Adult↗
PubMed1994

Occurrence of the nitrosamide precursor pyrrolidin-(2)-one in food and tobacco.

Pyrrolidinone was identified in food and tobacco samples by gas chromatography combined with NO-specific chemiluminescence detection (TEA). Up to 77 mg/kg pyrrolidinone were detected in cocoa powders, coffee, coffee surrogates, dried vegetables and tobacco leaves. When treated with excess nitrite under acidic conditions, N-nitrosopyrrolidinone was formed in concentrations up to 44 mg/kg. The nitrosation characteristics of pyrrolidinone indicate its possible conversion to nitrosopyrrolidinone under conditions of the gastric tract.

Cacao↗
PubMed1993

Caffeine-derived N-nitroso compounds. III: Mutagenicity in S. typhimurium and in vitro induction of DNA single-strand breaks in rat hepatocytes by mononitrosocaffeidine and dinitrosocaffeidine.

Mutagenesis in S. typhimurium and in vitro induction of DNA single-strand breaks in primary rat hepatocytes (DNA-SSB) have been investigated for two new N-nitroso compounds, mononitrosocaffeidine (MNC) and dinitrosocaffeidine (DNC). Mononitrosamidocaffeidine (MNAC) and tert.-(butyloxy)carbonyl-mononitrosamidocaffeidine (t-BOC-MNAC), both nitrosated derivatives of caffeidine with nitrosation at methylcarboxamide-N only, were also similarly studied. MNC, an asymmetric nitrosamine, failed to show mutagenicity in any of the tester strains used, and also did not induce DNA-SSB in rat hepatocytes. DNC, having both N-nitrosamide and N-nitrosamine groups in the molecule, showed direct mutagenicity in TA100, TA1535 and TA102. The mutagenic potential of the compound was found to increase on S9 activation. However, it was non-mutagenic in TA98 and TA1537. DNC also exhibited a high potential for inducing alkali-labile DNA-SSB in rat hepatocytes (70-78% C-T value) and was cytotoxic at concentrations over 0.1 mumole/ml. Both MNC and DNC were found to produce formaldehyde on S9 activation. MNAC was not mutagenic directly but showed weak mutagenicity on metabolic activation, whereas t-BOC-MNAC was mutagenic both with and without S9 activation in TA100, TA1535 and TA102. t-BOC-MNAC was more cytotoxic to hepatocytes than MNAC, though both caused DNA-SSB to the same extent (62% C-T value). On the basis of the presented data it is inferred that while DNC is a direct-acting mutagen in TA100, TA1535 and TA102 due to the presence of a reactive N-methylnitrosamido group, its mutagenic potential is greatly enhanced in the presence of S9 possibly due to the synergistic influence of an activated N-methylnitrosamino group in the molecule. Additionally, the study shows a qualitative consistency between Salmonella mutagenicity, genotoxicity in hepatocytes and the reactivity of the methyl group at the nitrosamido-N in nitrosated caffeidine compounds.

Animals↗
PubMed1993

Nitrosation of the antimicrobial drug hexetidine: nitrosamines derived from a triamine decomposition product.

Five new nitrosamines were identified as nitrosation products of N1,N3-bis(2-ethylhexyl)-2-methyl-1,2,3-propantriamine, a hydrolysis product usually found in preparations of the antimicrobial drug hexetidine. All nitrosamines are formed after deamination of the primary amino group by nitrosation of one of the two secondary amino groups. The propantriamine derivative is very easily nitrosatable, with total nitrosamine yields in the upper range of a comparative scale of drug nitrosatability.

Chromatography, High Pressure Liquid↗
PubMed1993

Preformed volatile nitrosamines in some Nigerian foodstuffs.

Some common Nigerian foodstuffs were assessed for their content of preformed volatile nitrosamine by chemiluminescence detection following gas chromatographic separation. Nitrosodimethylamine levels of between 0.4 and 4.6 ppb were detected in 75% of the samples analysed. The highest value was found in Brassica oleraceae, while Vernonia amygdalina contained the lowest detectable level. These data suggest that Nigerians may be exposed to chronic but very low levels of carcinogenic nitrosamines in their foods.

Brassica↗
PubMed1993

Monitoring nitrite, N-nitrosodiethanolamine, and mutagenicity in cutting fluids used in the metal industry.

We carried out an integrated environmental/biological monitoring program to evaluate cancer hazards among metal industry workers exposed to cutting fluids. Several cutting fluids were sampled according to response to a semiquantitative nitrite rapid test in metal factories in central Italy. The nitrite-positive samples were analyzed for nitrite and nitrosodiethanolamine (NDELA) content and mutagenic activity. The nitrite-negative samples were analyzed only for mutagenicity. Of the total samples, 20.6% were nitrite positive, and all contained NDELA. However, nitrite content was not quantitatively predictive of the NDELA content, which varied enormously among samples (0.3-1900 mg/kg). Nitrite-negative samples were always nonmutagenic. Mutagenicity was found in half the NDELA-containing samples but was not related to nitrite or NDELA content. Nitrite screening of cutting fluids in the field is an interesting method for identifying samples that potentially contain NDELA and other unknown mutagens and, when performed with short-term mutagenicity tests, nitrite screening seems to be a valid tool by which industrial managers and health officers could minimize the health hazards associated with occupational exposure to cutting fluids.

Diethylnitrosamine↗
PubMed1992

Effect of dietary nitrate on endogenous nitrosation of piperazine in humans.

The effect of dietary nitrate on endogenous nitrosation of a therapeutic dose of piperazine has been described in five human volunteers who acted as their own controls. The urinary excretion of endogenously formed N-nitro-somonopiperazine (MNPz) ranged between 9.2 and 80.1 micrograms/24 h on a normal uncontrolled diet which increased from 25.7 to 163.7 micrograms/24 h when the diet was supplemented with 250 mg nitrate. The corresponding urinary nitrate was 63.0-122.7 mg/24 h and 119.2-322.0 mg/24 h, respectively. The dinitroso derivative of piperazine was detected only in trace amounts and no detectable increase in its excretion was observed during high nitrate exposure. The unchanged piperazine (range 294-784 mg/24 h) in urine showed a decrease under high nitrate regimen (range 185-399 mg/24 h).

Carcinogens↗
PubMed1992

Caffeine-derived N-nitroso compounds--I: Nitrosatable precursors from caffeine and their potential relevance in the etiology of oesophageal and gastric cancers in Kashmir, India.

Salted tea prepared in Kashmir by adding sodium bicarbonate shows high methylating activity (equivalent to 3 p.p.m. N-methylnitrosourea) upon in vitro nitrosation. Pure caffeine treated under conditions of the tea preparation formed caffeidine and caffeidine acid. We report here the formation of two new compounds, mononitrosocaffeidine, an asymmetric nitrosamine, and dinitrosocaffeidine, a N-nitrosamide, on in vitro nitrosation of caffeidine. Mononitrosocaffeidine is also found after nitrosation of the typical Kashmir tea. The nitrosation of caffeidine acid produced N,N'-dimethyl-parabanic acid, mononitrosocaffeidine and N,N'-dimethyl-N-nitrosourea. In view of the well-known structure-activity relationships of these N-nitroso compounds, their possible endogenous formation due to high consumption of salted tea may be a critical risk factor for the high occurrence of oesophageal and gastric cancers in Kashmir.

Bicarbonates↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

Effects of long-term inhalation of N-nitrosodimethylamine in rats.

The toxicological evaluation and histopathological findings of a long-term inhalation study in progress with N-nitrosodimethylamine (NDMA) are presented. Exposure was to three concentrations of NDMA: 0.04, 0.2 and 1.0 ppm (corresponding to 120, 600 and 3000 micrograms/m3). A significant reduction in median survival time (nine months) was seen in animals treated with the highest concentration of NDMA. Tumours occurred mainly in the nasal cavity, with the highest incidences in the groups receiving 1.0 and 0.2 ppm NDMA (19/36 and 31/36 tumour-bearing animals); in the lowest exposure group, 13/36 nasal tumours have been observed. The survival time of this treatment group, however, was about two months longer than that of the controls.

Administration, Inhalation↗
PubMed1991

Metabolic denitrosation of N-nitrosamines: mechanism and biological consequences.

NADPH-dependent microsomal metabolism of N-nitrosamines results in both oxidative dealkylation and denitrosation of the molecule. For denitrosation, two enzymatic mechanisms have been proposed: (i) cytochrome P450 (P450)-dependent one-electron reduction of the nitrosamine molecule, resulting in the formation of nitric oxide (NO) and secondary and primary amine, and (ii) liberation of NO via an oxidative mechanism mediated by a P450-dependent one-electron abstraction. In order to clarify the mechanism of denitrosation, the metabolism and kinetics of N-nitrosodibenzylamine (NDBzA) and its corresponding secondary amine dibenzylamine were studied. The main metabolites of NDBzA are benzaldehyde, the primary amine benzylamine and nitrite. An important finding is that benzaldehyde is generated more rapidly from dibenzylamine than from the parent NDBzA. During reductive denitrosation of NDBzA, the oxygen atom in benzaldehyde is derived from air, while benzaldehyde generated via the oxidative mechanism of denitrosation receives its oxygen atom from water due to hydrolysis of the intermediary benzylidenebenzylamine. Microsomal incubation of NDBzA in buffer containing 18O-H2O resulted in no incorporation of 18O from water into benzaldehyde, which could be related to the formation of the corresponding benzaldehyde, which could be related to the formation of the corresponding benzylidenebenzylamine. It is concluded that NDBzA is denitrosated by the proposed reductive mechanism. Current belief is that denitrosation leads to detoxification of the NA molecule; however, toxic effects cannot be excluded if the conversion of NO into NO2- and NO3- involves intermediary formation of the NO2 radical.(ABSTRACT TRUNCATED AT 250 WORDS)

Biotransformation↗