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At least 883 records · Page 49Linked to original sources
PubMed1987

Potassium perchlorate, potassium iodide, and propylthiouracil: promoting effect on the development of thyroid tumors in rats treated with N-bis(2-hydroxypropyl)-nitrosamine.

The effect of 1000 ppm potassium perchlorate (KClO4), 1000 ppm potassium iodide (KI) or 1000 ppm propylthiouracil (PTU) in the diet on the development of thyroid tumors was studied histologically and biochemically in Wistar rats given a single ip injection of 280 mg of N-bis(2-hydroxypropyl)nitrosamine (DHPN) per 100 g body weight. Basal diet containing 100 ppm KClO4, 1000 ppm KI or 1000 ppm PTU was given for 19 weeks from week 2 to week 20. The incidence of thyroid adenomas at the end of week 20 of the experiment was 100% (20/20) in rats treated with DHPN followed by KClO4, 85% (17/20) in rats given DHPN followed by KI, 95% (19/20) in rats given DHPN followed by PTU, and 5% (1/20) in rats given DHPN alone. The incidence of thyroid cancers was 100% (20/20) in rats treated with DHPN followed by KClO4, 65% (13/20) in rats treated with DHPN followed by KI and 0% (0/20) in rats treated with DHPN followed by or not followed by PTU. Rats given KClO4, KI or PTU alone and untreated rats had no thyroid tumors. The mean values of TSH in serum were 2.94 +/- 0.79 ng/ml in rats treated with DHPN followed by KClO4, 9.40 +/- 16.0 ng/ml in rats treated with DHPN followed by KI and 60.94 +/- 20.60 ng/ml in rats treated with DHPN followed by PTU. It was confirmed that (1) KClO4, PTU and KI promote the development of thyroid tumor in rats treated with DHPN, (2) the promoting effect of KClO4 or KI is stronger than that of PTU and (3) the value of TSH in serum is not parallel to the promoting effect on the development of thyroid tumor.

Animals↗
PubMed1987

Effect of N-ethyl-N-butyl-nitrosamine on the esophageal mucosa of the rat. Histometric investigation of early tumor stages.

80 male Wistar rats received an oral ad libitum application of N-ethyl-N-butyl-nitrosamine in a concentration of 0.18 g per litre of drinking water. The changes induced in the esophageal mucosa and determined at three intervals (up to 48 days, up to 91 days, and up to 112 days after commencement of carcinogen exposure) were compared by microscopy with the results from a control group of 10 male Wistar rats of the same age. Several histomorphometric parameters were investigated with the aid of a Leitz ocular micrometer. The earliest localized changes found were an increase in the thickness of the epithelium and the horny layer, and an elongation of the papillary bodies and a widening of the parabasal cellular layer. Later--with a substantial increase in the rate of mitosis in all layers of the epithelium, there was a significant thickening of the non-papillomatous and papillomatous epithelium, an enlargement of the nuclei, especially in the middle and upper layers of the epithelium and a thickening of the horny layer, parts of the latter being parakeratotic. The papillomatous changes corresponded in some cases to moderate epithelial dysplasias. As expected, no fully-developed invasive carcinomas occurred in the early period investigated. The histometric data permit the conclusion to be drawn that the lesions described are demonstrable not only at the exophytic-papillomatous epithelium but also in multifocally localized form at the flat, non-papillomatous mucosa, and that they can definitely be regarded as the expression of an incipient field cancerification.

Animals↗
PubMed1986

The effect of age on susceptibility of rats to carcinogenesis by two nitrosamines.

The carcinogenic effects of identical doses of two carcinogenic nitrosamines each given to young (8-week-old) and old (54- or 65-week-old) F344 rats were compared. The two compounds were nitrosomorpholine, which was given in drinking water to females, and nitrosobis(2-oxopropyl)amine (BOP), which was given to males by gavage in oil. In both old (54 weeks) and young rats nitrosomorpholine at 100 mg/liter induced hepatocellular neoplasms in the liver of almost all rats, but the rate at which the neoplasms killed the animals was much slower in the old than in the young rats, and by this measure of potency the old rats given 100 mg/liter resembled young rats given 40 mg/liter. BOP administered at two dose rates, 2.5 mg twice a week for 35 weeks, and 6 mg twice a week for 29 weeks, induced neoplasms of the lung and of follicular cells in the thyroid and transitional cell neoplasms of the bladder and kidney pelvis in almost all animals when treatment began at 8 weeks, but many fewer, or none, of these neoplasms in male rats whose treatment began at 65 weeks. Instead, the old male rats developed hepatocellular neoplasms in the liver, none of which were seen in the young rats treated with BOP. There was no significant difference in mortality rate between young and old rats which would account for these differences in BOP-treated rats.

Age Factors↗
PubMed1987

Soft agar colony formation of bladder cells during carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine and application to detection of bladder cancer promoters.

N-Butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was given to male Fischer 344 rats at a dose of 0.05% in drinking water for 2, 4, 6 and 12 weeks, and double soft agar colony formation of the uroepithelial cells was determined periodically, during and after this administration. In the group administered BBN for 2 weeks, no significant colony growth was observed until week 8. In the group given BBN for 4 weeks, colony growth was observed at week 4 and the numbers of colonies remained constant until week 8. In the group given BBN for 6 weeks, significant colony growth was observed at weeks 6 and 8. In the group on BBN for 12 weeks, colonies grew from week 4 and significant numbers of colonies were observed from week 6, increasing up to week 10. Colony formation preceded papilloma development in the rat bladder, and was dependent on the duration of BBN administration. The effect of amino acids and sodium saccharin on colony formation was also evaluated. The rats were given 0.05% BBN for 3 weeks, followed immediately by the administration for 9 weeks of 2% L-tryptophan, 1% D-tryptophan, 2% L-leucine, 2% D-leucine, 2% DL-leucine, 2% L-isoleucine, 2% DL-isoleucine or 5% sodium saccharin in the diet. At week 12, the numbers of colonies were significantly higher in the groups given sodium saccharin, L-leucine, DL-leucine, L-isoleucine, DL-isoleucine and D-tryptophan. This method provides a potentially useful approach toward analyzing the early events in bladder carcinogenesis and may be applicable to detect new bladder carcinogens and promoters.

Animals↗
PubMed1987

Inhibition of N-butyl-N-(4-hydroxybutyl)nitrosamine-induced rat urinary bladder carcinogenesis by alpha-difluoromethylornithine.

The effect of oral administration of alpha-difluoromethylornithine (DFMO), an irreversible ornithine decarboxylase inhibitor, on N-butyl-N-(4-hydroxybutyl)nitrosamine (BHBN)-induced rat urinary bladder carcinogenesis was investigated. Four-wk-old male Fischer 344 rats, 30-38 per group, were divided into 3 groups; each group was divided into 3 subgroups. In Group A, 6-wk treatment with 0.05% BHBN in drinking water was followed by either 0.5% (A1), 0.2% (A2), or 0% (A3) DFMO in drinking water for 34 wk. In Group B, coadministration in drinking water of 0.01% BHBN and either 0.5% (B1), 0.2% (B2), or 0% (B3) DFMO was continued for 30 wk. Group C consisted of animals receiving 0.5%, 0.2%, or 0% DFMO in drinking water for 34 wk without prior or cocarcinogen treatment. Bladder tumorigenesis was clearly inhibited by DFMO; tumor incidence was 14 of 37 (38%) in A1, 16 of 38 (42%) in A2, and 31 of 35 (89%) in A3, and 7 of 35 (20%) in B1, 14 of 35 (40%) in B2, and 28 of 35 (80%) in B3 (P less than 0.01, DFMO groups as compared to the respective control A3 or B3). The average tumor volume was strikingly reduced in Group A rats given DFMO (3.0 mm3 in A1, 5.0 in A2, and 38.6 in A3). Significant suppression of tumor multiplicity (number of tumors/tumor-bearing bladder) was observed in DFMO-treated subgroups in Group B (1.1 in B1, 1.3 in B2, and 1.8 in B3). In both Groups A and B, however, DFMO failed to suppress hyperplastic changes (simple hyperplasia) or preneoplastic lesions (nodulopapillary hyperplasia). Systematic examination of all pertinent organs excluding the brain showed no adverse effects attributable to DFMO treatment except for decrease in body weight (less than 7%), which was consistently observed in the groups receiving 0.5% DFMO, and reduction in the combined weight of the prostate and seminal vesicles (less than 20%), which was noted in Group B in which exposure to DFMO was started at a younger age. These results indicate that oral administration of DFMO is quite effective in suppressing (or retarding) BHBN-induced carcinogenesis with minimal untoward effects and confirm the similar inhibitory effects demonstrated earlier with the heterotopically transplanted rat urinary bladder system.

Administration, Oral↗
PubMed1987

Effects of castration before and after treatment with N-bis (2-hydroxypropyl)-nitrosamine (DHPN) on the development of thyroid tumors in rats treated with DHPN followed by phenobarbital.

The effect of castration on the development of thyroid tumors was studied histologically and biochemically in Wistar rats given a single ip injection of 210 mg of N-bis (2-hydroxypropyl)-nitrosamine (DHPN) followed by phenobarbital (Pb). Castration was performed one week after, or one week before the injection of DHPN. The injection of DHPN was given at the end of the first week, and the rats were fed 500 ppm Pb in the basal diet for 38 weeks from week 3 to week 40. The incidence of thyroid adenomas and cancers was 20% (4/20) and 10% (2/20) in rats treated with DHPN alone. It was 75% (15/20) and 40% (8/20) in rats treated with DHPN and Pb; 30% (6/20) and 15% (3/20) in rats treated with DHPN and Pb, and castrated after DHPN; 20% (4/20) and 0% in rats treated with DHPN and Pb, and castrated before DHPN and Pb; and 0% and 0% in rats castrated either before or after receiving DHPN. Castration thus inhibited the development of thyroid tumor in rats treated with DHPN. The inhibition of tumor development in rats treated with DHPN and Pb, and castrated before receiving DHPN, was greater than in the rats castrated after receiving DHPN. Castration inhibited the secretion of TSH in rats treated with DHPN and Pb.

Animals↗
PubMedDate not supplied

[Carcinogenic nitrosamine content of food products of the Moldavian SSR].

The authors provide data concerning the content of carcinogenous N-nitrosocompounds in foods manufactured in the Moldavian SSR. Over 100 samples of foods of both vegetable and animal origin have been analyzed. It has been found that foods manufactured in the Moldavian SSR are contaminated with carcinogenous N-nitrosamines but to an insignificant degree. It is concluded that the degree of a relative risk may be regarded as negligible.

Food Contamination↗
PubMed1988

Effect of 1-hexylcarbamoyl-5-fluorouracil on development of rat urinary bladder tumor induced by N-butyl-N-(4-hydroxybutyl)nitrosamine.

The present study was conducted to examine the effect of 1-hexylcarbamoyl-5-fluorouracil (HCFU) on the development of urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in rats. One hundred twenty male Fischer 344 rats were divided into 6 groups. Sixty rats (groups 1, 2 and 3) were given 0.05% BBN in drinking water for the initial 8 weeks of the experiment and another 60 rats (groups 4, 5 and 6) served as controls. HCFU mixed in the powder diet was administered at daily doses of 100 mg per kg of body weight. Group 2 received HCFU throughout and group 3 after BBN administration for 8 weeks. All animals were sacrificed at 20 weeks from the beginning of the experiment and examined histopathologically. In groups 1, 2 and 3, urinary bladder tumors developed in 13 of 18, 0 of 20, and 4 of 19, respectively. Incidences of tumors in the 2 groups treated with HCFU were significantly lower than that of group 1 treated with BBN alone. These results indicated that HCFU was effective in suppressing the incidence of bladder tumor.

Animals↗
PubMed1988

Theoretical QSAR study on carcinogenic potency of N-nitrosamines.

A mechanistic QSAR study on N-nitrosamines (NA) was performed with the aid of the semiempirical MINDO/3 method. Both the chemical reactivity and the transport in biological medium were taken into account. The parent NA molecules and their first reaction intermediates in the metabolic activation pathway were examined for possible determinants of the relative carcinogenic potency. The correlations found support the previous suggestions concerning the metabolic C alpha radical hydroxylation of NA. The role of transport properties in the early stage of NA biotransformation was also demonstrated.

Biotransformation↗
PubMedDate not supplied

[Content of N-nitrosamines in Soviet food products].

The author presents the results of the analysis of N-nitrosamine (NA) content in animal and vegetable products from various regions of the country. The causes of NA formation from their precursors during technological treatment and possible ways of its prevention have been discussed.

Animals↗
PubMed1987

Aging and urinary bladder carcinogenesis induced in rats by N-butyl-N-(4-hydroxybutyl)nitrosamine.

The effect of age on induction of carcinogenesis by N-butyl-N-(4-hydroxybutyl)nitrosamine [(BBN) CAS: 3817-11-6] in the urinary bladder epithelium was examined in 130 male and 130 female F344 rats. Rats of both sexes 6, 52, and 98 weeks old were given 0.025% BBN in their drinking water for 20 weeks. Then approximately half the rats were sacrificed, while the rest were maintained without further treatment for 10 weeks. Examination of the rats revealed an age-related increase in the induction of urinary bladder carcinoma, although the total intakes of BBN and urinary excretions of its proximate carcinogen were not age related. Rats treated with BBN at 98 weeks of age developed more squamous cell carcinomas and invasive carcinomas than the 2 younger groups. This study demonstrated an increased risk of urinary bladder carcinogenesis with age in animals.

Aging↗
PubMedDate not supplied

Analysis of selected drug formulations for volatile nitrosamines.

A number of selected drug formulations on the Canadian market were analyzed for N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) content by using a gas chromatograph interfaced to a thermal energy analyzer (GC/TEA). Of the 34 formulations analyzed, NDMA was found in 21 at levels up to 12 ppb and NDEA was found in 11 at levels up to 0.6 ppb. In many cases, the drug entity in the formulation did not contain the precursors for the observed nitrosamines.

Chromatography, Gas↗
PubMed1987

Strong promoting activity of reversible uracil-induced urolithiasis on urinary bladder carcinogenesis in rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

The tumor-promoting effect of uracil-induced calculi on rat urinary bladder carcinogenesis was investigated in male F344 rats pretreated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Since uracil-induced calculi and papillomatosis of the bladder are reversible, uracil was given for a limited period after the treatment with BBN. Animals were given 0.05% BBN in their drinking water for 4 wk and then treated with uracil as 3% of the diet for 8 or 16 wk. After the uracil treatment, rats were given basal diet without uracil until Wk 28 of the experiment. Animals were killed from each group at the end of either Wk 12, 20, or 28. The incidence of carcinoma of the bladder was 40% after only 8 wk of uracil treatment following BBN initiation and increased to 100% when uracil treatment was extended to 16 wk. After discontinuation of uracil treatment, the papillomatosis disappeared, but the incidence of carcinoma steadily increased with increasing time. In the control group given BBN alone, only 1 of 16 rats had carcinoma at Wk 28. The present findings clearly demonstrate that uracil-induced urolithiasis had a strong promoting activity on BBN bladder carcinogenesis.

Animals↗
PubMed1987

The ferret as a model for endogenous synthesis and metabolism of N-nitrosamines.

We have begun to evaluate the ferret as a model for studying gastric nitrosation and nitrosamine metabolism. Jugular cannulation allows convenient dosing and sampling of blood, and this technique has been used to study clearance of N-nitrosodimethylamine (NDMA) after intravenous, intraperitoneal and intragastric administration. NDMA metabolism can be inhibited by 4-methylpyrazole for up to 24 h; the accumulation of endogenously-synthesized NDMA can therefore be observed in animals following pretreatment with this compound. We have studied endogenous NDMA synthesis in animals dosed with dimethylamine and nitrite and in animals to which no NDMA precursors were administered.

Animals↗
PubMed1987

Laser photofragment spectroscopy: a new technique for the detection of N-nitrosamines and other nitroso compounds.

The potential of laser photofragment spectroscopy (LPS) for the detection and discrimination of nitrosamines, alkyl nitrites, thionitrites and C-nitroso compounds has been evaluated. The technique combines high sensitivity with the dramatic specificity of high-resolution spectroscopy and utilizes pulsed laser photodissociation with synchronized detection of the NO photofragment by laser-induced fluorescence (LIF). Using supersonic molecular beam sampling and wavelength tunable photodissociation, LPS can generate well-resolved finger-print spectra characteristic of the parent nitroso compound.

Lasers↗
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

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↗
PubMed1987

N-nitrosamines and nitrosatable compounds in rubber nipples, pacifiers and other rubber and plastic commodities.

In 1983 and 1985, rubber teats and pacifiers from the Dutch market were analysed for N-nitrosamines (NA) and nitrosatable compounds (NC) by extraction with an artificial saliva test solution (24 h, 40 degrees C). NC were determined as NA (gas chromatography-thermal energy analysis) after nitrosation. In 1983, the total content of NA and NC varied from 4-40 micrograms/kg and 50-3700 micrograms/kg, respectively (18 samples). In 1985, NA and NC varied from 3-94 micrograms/kg and 26-5100 micrograms/kg, respectively (20 samples). According to Dutch legislation, teats may contain no more than 1 microgram/kg and 20 microgram/kg NA and NC. Of other rubber and plastic commodities analysed, balloons contained levels of up to 120 micrograms/kg and 2800 micrograms/kg NA and NC.

Cooking and Eating Utensils↗