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Biomedical subjects

A R Tricker

Publications and source records attributed to A R Tricker.

At least 55 records · Page 3Linked to original sources
PubMed1990

Mutagenic and genotoxic activities of extracts derived from the cooked and raw edible mushroom Agaricus bisporus.

A. bisporus has been reported to be carcinogenic to mice [Toth et al. (1986) Cancer Res 38:177-180] and mutagenic in Salmonella typhimurium [Sterner et al. (1982) Mutat Res 101:269-281]. The effects of different heat treatments on the mutagenicity of raw, cooked (boiled) and fried A. bisporus extracts in the S. typhimurium test is reported. The spectrum of potential mutagenic activity of A. bisporus extracts was tested in vitro in Syrian hamster embryo cells for selective DNA amplification and in primary rat hepatocytes for DNA single-strand breaks. DNA single-strand breaks were also determined in liver cells of rats and micronuclei were measured in bone marrow cells of mice in vivo following oral application of A. bisporus extracts. It was shown that the complex A. bisporus extracts per se are not detectably mutagenic in S. typhimurium and that the previously observed increase in number of colonies per plate is probably due to a histidine artefact. No indication of genotoxicity was seen in the two in vitro assays with primary mammalian cells with two different end points. No evidence of in vivo genotoxic effects was observed in the rat liver cells. Finally, A. bisporus was not genotoxic in the micronucleus assay of mouse bone marrow cells in contrast to its previously reported carcinogenicity in mice.

Agaricus↗
PubMed1990

Ureterosigmoidostomy: long-term results, risk of carcinoma and etiological factors for carcinogenesis.

We followed postoperatively 75 patients who underwent ureterosigmoidostomy between 1942 and 1987. Of the patients 30 were asked to undergo routine examination, including fiberoptic sigmoidoscopy with biopsy and analysis of a urine-feces slurry for nitrate, nitrite and nitrosamines in comparison to 20 control volunteers. After a mean observation of 14 years 7 months (1 to 46 years) 64.5% of the patients had bilaterally normal kidneys without any previous complications, 77.5% of the renal units being normal. Sigmoidoscopic biopsy revealed 3 carcinomas at the ureterocolonic junction resulting in an 8.5 to 10.5-fold increased risk of colon carcinoma compared to the general population. The excretion of nitrite and N-nitrosamines was increased, and nitrate excretion was decreased compared to healthy control volunteers, suggesting endogenous formation of nitrosamines by bacterially reduced nitrate and endogenous amines. The urological long-term results of ureterosigmoidostomy are similar to those of conduits. However, the increased incidence of colon carcinoma is not yet proved to be higher than in conduits.

Adult↗
PubMed1989

The occurrence of N-nitroso compounds in kiwam tobacco.

The concentrations of tobacco-specific nitrosamines (TSNA), volatile and non-volatile N-nitroso compounds in kiwam, a fermented Indian tobacco product are presented. Total identified N-nitroso compound concentrations in kiwam ranged from 6.19 to 25.4 mg/kg fresh weight tobacco, the concentration range of TSNA was 5.43-22.2 mg/kg tobacco which accounted for 67-87% of the total identified N-nitroso compound burden. The high concentrations of TSNA found in kiwam tobacco may present a considerable exposure source to carcinogenic N-nitroso compounds for people using this type of tobacco.

India↗
PubMed1989

Increased urinary nitrosamine excretion in patients with urinary diversions.

Tumor development at the site of ureterointestinal anastomosis is a recognized complication in patients with continent urinary diversions. Aerobic cultures of rectal urine samples from 30 patients with urinary diversions (26 ureterosigmoidostomies, two colon conduits, one ileal conduit and a Gersuny bladder) showed a complex bacterial flora containing nitrate-reducing organisms (Escherichia coli, Proteus and Klebsiella spp.). In comparison to normal bladder urine samples from control volunteers (n = 20), rectal urine samples from ureterosigmoidostomy patients (n = 26) showed a significant decrease (P less than 0.0001) in urinary nitrate (0.93 +/- 0.39 versus 0.27 +/- 0.23 mmol/l), a significant increase (P less than 0.0001) in urinary nitrite (not detected versus 29.24 +/- 39.93 mumol/l) as well as a significant increase (P = 0.013) in urinary N-nitroso compound excretion (57.33 +/- 33.87 versus 93.96 +/- 65.76 nmol/l). Significant increases were also found for the urinary excretion of individual volatile and non-volatile N-nitroso compounds, clearly demonstrating a bacterially mediated in vivo formation of N-nitroso compounds in the 'colon' bladders of patients with urointestinal diversions that may be an important etiological risk factor for colon carcinogenesis in this patient group.

Bacteria↗
PubMed1989

Urinary excretion of nitrate, nitrite and N-nitroso compounds in Schistosomiasis and bilharzia bladder cancer patients.

Saliva and 24-h urine samples were collected from male Schistosomiasis (bilharzia) patients with S. haematobium infection and possible concurrent S. mansoni infection without diagnosed bladder cancer (n = 27), bilharzia patients with diagnosed bladder cancer (n = 23) as well as a comparative control group (n = 27) of healthy Egyptian volunteers with no current bilharzia infection and/or bacterial urinary tract infections from the Nile Delta area of Egypt. Saliva samples were analysed for the presence of nitrate and nitrite; urine samples were analysed for the presence of nitrate, nitrite, volatile and non-volatile N-nitroso compounds. Bilharzia patients prior to, and after, diagnosed bladder cancer regularly excreted free nitrite as well as volatile nitrosamines (N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosopiperidine and N-nitrosopyrrolidine) in addition to which elevated concentrations of non-volatile N-nitrosamino acids (N-nitrosoproline, N-nitrososarcosine, N-nitrosothiazolidine-4-carboxylic acid and its 2-methyl derivative) were also present. Total urinary excretion of volatile N-nitroso compounds (0.32 +/- 0.64 micrograms/day; mean +/- SD) and non-volatile N-nitroso compounds (31.20 +/- 22.07 micrograms/day) was observed in the Egyptian control group. Significantly higher concentrations were found in bilharzia patients: 3.47 +/- 6.42 (P less than 0.05) and 62.91 +/- 21.96 (P less than 0.05); as well as in bilharzia patients with diagnosed bladder cancer: 1.71 +/- 1.96 (P less than 0.02) and 44.94 +/- 7.31 respectively. Free nitrite was found in the urine of two volunteers in the Egyptian control group (1.7 and 3.0 micrograms/day), urinary nitrite was significantly increased in bilharzia patients (5.18 +/- 9.11 micrograms/day, P less than 0.02) and in bladder cancer patients (1.75 +/- 2.81 micrograms/day, P less than 0.05). Nitrate concentrations were elevated from 139.3 +/- 82.2 in the control group to 143.6 +/- 136.3 and 175 +/- 190 in the bilharzia and bladder cancer groups respectively. These results indicate that significant in vivo formation of nitrite and volatile N-nitroso compounds occurs in the urinary bladder of bilharzia patients and this may be an oetiological factor in the induction of bilharzial bladder cancer associated with S. haematobium infection.

Adult↗
PubMed1989

Mutagenicity and carcinogenicity of smoked meat from Nagaland, a region of India prone to a high incidence of nasopharyngeal cancer.

The incidence of nasopharyngeal cancer (NPC) in the northeastern part of India is reported to be high. A possible correlation between consumption of smoked meat by the tribal people and high suceptibility to NPC has been postulated. The charred portion of smoked beef and meat of other animals was collected from this area, extracted with acetone and the extract (SME) was tested using the Ames test as well as for chromosomal aberration in mouse bone marrow cells and carcinogenicity using Swiss bare mice. It was observed that SME was mutagenic in all five strains of Salmonella typhimurium (TA98, TA1538, TA100, TA1535 and TA1537), with or without S9 mix, and was clastogenic in a mammalian test system. SME also has the potential to induce skin papilloma as well as systemic tumours in Swiss bare mice. Chemical analysis of SME revealed the presence of low concentrations of volatile nitrosamines.

Animals↗
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

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↗
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

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↗
PubMed1986

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

Nitrosation of dipeptides which do not contain imino acids leads to rearrangement and the formation of N-nitrosoiminodialkanoic acids. The optimum conditions for the nitrosation of dipeptides in buffer solutions occur at pH 2.0 (0.8-3.2% yield) and are not significantly catalysed by thiocyanate. In vitro nitrosation in gastric juice resulted in a lower yield. It was demonstrated that under normal gastric conditions, a maximum yield of 0.1 mumol total N-nitrosoiminodialkanoic acids/0.1 mol dipeptide would occur, 0.1 mol representing a typical dietary intake of dipeptide. This corresponds to a total concentration of approximately 20 micrograms/l N-nitrosoiminodialkanoic acids over a 24 h period. However, this figure may be significantly altered due to the fluctuation of nitrosation catalysts and inhibitors in gastric juice. Further studies showed that N-nitrosoiminodialkanoic acids are quantitatively excreted in urine when fed by gavage to rats. However, co-administration of the precursor dipeptide and nitrite resulted in negligible in vivo formation. The presence of N-nitrosoiminodialkanoic acids in normal human urine was not detected. Thus it was concluded that the monitoring of N-nitrosoiminodialkanoic acids in human urine is not a suitable method for biological monitoring of the endogenous nitrosation of dipeptides.

Animals↗
PubMed1985

Some nitrosoamino acids in bacon adipose tissue and their contribution to the total N-nitroso compound concentration.

The levels of nitrosoamino acids and apparent total N-nitroso compounds in the adipose tissue of raw bacon have been examined. Nitrosoamino acids were detected in 80% of the samples in levels of up to 0.2 mg/kg. Apparent total N-nitroso compounds were present in all samples in concentrations of between 0.4 and 3.7 mg (N-NO)/kg. Nitrosoamino acids accounted for approximately only 1% of the apparent total N-nitroso compounds. The majority of the apparent total N-nitroso compounds in the adipose tissue were associated with the insoluble connective tissue fraction, with the remainder present as chloroform soluble species.

Adipose Tissue↗