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At least 937 records · Page 52Linked to original sources
PubMed1978

Effect of phenacetin and caffeine on the urinary bladder of rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

The effect of phenacetin and caffeine on urinary bladder carcinogenesis in rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was examined. Animals were given a high or low dose of BBN for 4 weeks and then phenacetin or caffeine was administered for 30 or 32 weeks, respectively. All the animals were examined histologically after 36 experimental weeks. The incidence of papillary or nodular hyperplasia, papilloma, and cancer of the urinary bladder was significantly higher in the groups treated with BBN and then with phenacetin than in those treated with BBN alone, especially with a high dose of BBN. Simple hyperplasia and papillary or nodular hyperplasia developed in the urinary bladder of rats treated with phenacetin alone. Papillary proliferative growth of the renal pelvis was seen in one rat treated with a low dose of BBN and phenacetin. Treatment with caffeine after BBN had no enhancing effect and caffeine alone caused no remarkable changes.

Animals↗
PubMed1984

Rapid induction of carcinoma in situ in dog urinary bladder by sequential treatment with N-methyl-N'-nitrosourea and N-butyl-N-(4-hydroxybutyl)-nitrosamine.

A highly atypical intraepithelial proliferation, which was interpreted as carcinoma in situ, developed in the urinary bladder of 2 beagle dogs after repeated intravesical instillations of N-methyl-N'-nitrosourea followed by oral administration of N-butyl-N-(4-hydroxybutyl)nitrosamine. The latent period was 37 weeks. The technique may provide a useful model to study the natural history of bladder cancer, particularly carcinoma in situ.

Animals↗
PubMed1978

Chemical models for possible nitrosamine artifact formation in environmental analysis.

Preliminary data concerning two different phenomena of potential importance to those studying the analysis and formation of environmental N-nitroso compounds are presented. First of all, we report that inorganic nitrite in the solid phase can serve as an effective nitrosating agent for solutions of amines in certain nonaqueous media. Secondly, we describe evidence suggesting that the appearance of nitrosamines as contaminants in deionized water (Cohen, 1977; Gough et al., 1977; Fiddler et al., 1977) might result at least partly from simple, acid-catalyzed nitrosation of the amine/ammonium functional groups on the anion exchange resins used in the demineralization process. Possible implications of both phenomena are discussed and potentially useful measures for their control are suggested.

Catalysis↗
PubMed1982

[Effect of cis-diamminedichloroplatinum (II) (CDDP) on bladder cancer on rats induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)].

The effect of CDDP was studied on rat bladder tumors induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN). A total of 140 rats was divided into 7 groups and 0.05% BBN in drinking water was given for 8 weeks. Half doses of LD50 of CDDP, mitomycin C, cyclophosphamide were injected to rats at the 16th or 20th experimental week. All rats were sacrificed at the end of 24 weeks and bladders were removed. Each of the groups receiving anticancer drugs had significant reduction in mean tumor number per rat compared to the control group (p less than 0.05). CDDP was the most effective in reducing tumor size when it was administered at the 16th week (p less than 0.01).

Animals↗
PubMed1983

[Experimental administration of di-N-butyl-nitrosamine (DBN) in rats. Carcinogenic activity in the urinary bladder].

Di-N-butyl-nitrosamine (DBN) was administered in a suspension with dimethylsulfoxide (DMSO) to 80 rats in doses of 10 and 40 mg/kg/day. The carcinogen was given to the animals in groups of 40 either orally or subcutaneously. The animals were exposed to the carcinogen for a maximum of 320 days. In one group of animals, hypertrophia and hyperplasia affected the whole epithelium of the bladder. In the other group, hyperplasia was intense enough to be considered as carcinomatous. A third group developed papillomatous carcinomas, which occupied the whole interior of the bladder.

Animals↗
PubMed1983

Metabolism of tobacco-specific nitrosamines by cultured rat nasal mucosa.

The metabolism of two nasal carcinogens, N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), was investigated using cultured nasal septa of F344 rats. The explants were cultured with 14C-labeled N-nitrosamines, and unbound metabolites present in the medium were quantitated by high-performance liquid chromatography. The results indicated that the mucosa of the nasal septum had a marked capacity to metabolize NNN and NNK to hydroxylated products which were released into the culture media. Extensive activation by alpha-carbon hydroxylation of NNN (preferentially 2'-carbon hydroxylation) and NNK was observed, whereas no deactivation by pyridine N-oxidation could be detected. Microautoradiographic studies of explants showed that binding of radioactivity occurred preferentially in the respiratory and olfactory epithelia and in the subepithelial glands of the nasal mucosa. The results suggest that reactive metabolites of NNN and NNK are formed within the target tissue rather than being transported from the liver to the nasal mucosa. The results also show that the culture of nasal septa can be used to ascertain the role of the nasal mucosa in the activation of nasal-specific carcinogens.

Animals↗
PubMed1982

Tobacco specific N-nitrosamines: occurrence and bioassays.

A new GC-TEA method for the analysis of tobacco-specific N-nitrosamines (TSNA) has been developed. Four TSNA have thus far been identified; these are N'-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N'-nitrosoanatabine (NAT) and N'-nitrosoanabasine (NAB). The method is currently being applied to the development of cigarette filter-tips which will selectively remove these carcinogens from cigarette smoke. Since recent epidemiological studies have established a correlation between snuff dipping and oral cancer, we have analysed leading snuff brands for TSNA. Snuff products from Sweden, Denmark, Bavaria and the USA contained 5-106 mg/kg of the TSNA and the saliva of snuff dippers had TSNA levels of 20-890 micrograms/kg. NNN, NNK and NAB induce benign and malignant tumours of the respiratory tract of mice and rats. We have shown that NNN and NNK induce tumours in the upper respiratory tract of hamsters and that NNK is the most active carcinogen of the TSNA, also inducing adenoma and adenocarcinoma in the hamster lung. The reported chemical analyses and bioassay results support the epidemiological findings on the causal association of tobacco use and cancer in man.

Adult↗
PubMed1980

Dose response of saccharin in induction of urinary bladder hyperplasias in Fischer 344 rats pretreated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

Studies were made on the dose response of saccharin in the induction of bladder lesions. Inbred F344 rats of both sexes were pretreated with 100 ppm N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in the drinking water for 4 weeks. Sodium saccharin was given at 50,000, 10,000, 2,000, and 400 ppm in the diet for 32 weeks after BBN administration, and surviving rats were killed at the end of week 36 of the experiment. No increase in incidence of papilloma or cancer was noted in either sex at any dose of saccharin after BBN as compared to levels induced by BBN alone. The incidences of two types of hyperplasia and average number of papillary or nodular hyperplasias per 10 cm of basement membrane were significantly increased in the group receiving 50,000 ppm saccharin as compared to the group given BBN only. None of the incidences or numbers of these lesions were significantly different in any of the other saccharin-treated groups when compared to the group treated with BBN alone except for the incidences of two types of hyperplasias in the female rats dosed with 10,000 ppm saccharin. Dose-response curves showed enhanced hyperplastic responses in both sexes given 2,000--50,000 ppm saccharin. Administration of various doses of saccharin without BBN did not cause any changes in the urinary bladders of rats of either sex. These results show that saccharin enhances the induction of early-stage bladder lesions and that the biologic response demonstrates a dose-response effect.

Animals↗
PubMed1982

[Use of the bacterial flocculation test for assessing the mutagenic properties of carcinogenic nitrosamines and nitramines].

Fluctuation test developed by Green allows to detect the mutagenicity of trace and non-toxic chemical concentrations. Mutagenic activity of both carcinogenic nitramines--nitrodimethylamine, nitrodiethylamine and nitromorpholine (0.1--10 mM) and their nitrosamine analogues-nitrosodimethylamine, nitrosodiethylamine and nitrosomorpholine (0.01--0.1 mM) was detected in fluctuation test with Salmonella typhimurium TA 98 and TA 1530 as indicator organism in the presence of postmitochondrial supernatant from liver of rats treated with Aroclor 1254. Nearly all compounds appeared to be mutagenic even in the absence of co-factors of microsomal oxygenation.

Aniline Compounds↗
PubMed1978

Effect of dose on the carcinogenic activity of orally administered N-bis(2-hydroxypropyl)nitrosamine in rats.

The carcinogenic activity of orally administered N-bis(2-hydroxypropyl)-nitrosamine (DHPN) in male Wistar rats was evaluated with respect to its dose. DHPN was administered at two doses, 100 ppm and 500 ppm, in the drinking water to rats for 25 to 52 weeks. Tumors developed in the lung, liver, and thyroid of rats receiving 100 ppm DHPN and in the lung, liver thyroid, esophagus, kidney, and urinary bladder of rats receiving 500 ppm DHPN. The principal target organ was the lung in rats receiving either 100 or 500 ppm DHPN, indicating that the carcinogenic action of these doses of DHPN was similar to that of higher doses previously reported. Histologically, the tumors were adenoma, adenocarcinoma, squamous cell carcinoma, and combined carcinoma of the lung, hepatocellular carcinoma and hemangioma of the liver, adenoma and adenocarcinoma of the thyroid, squamous cell papilloma and carcinoma of the esophagus, renal cell and transitional carcinoma of the kidney, and transitional cell carcinoma of the urinary bladder. No pancreatic tumors were observed.

Adenocarcinoma↗
PubMed1982

[Toxic effects of nitrosamines with respect to marine organisms].

Nitrosamins present in the aquatic medium are considered as carcinogenic substances to the laboratory animals. This experimentation has for object to precise toxicity effects of the nitroso-compounds: nitrosodimethyllamine (NDMA) on two phytoplankton cultures, and on the common mussels. The addition of NDMA to the seawater of aquarium, in particular experimental conditions induces toxicity effects on the growth and behavior of phytoplanktonic cultures and of the common mussels: Mytilus edulis (tissus modification, and attack of some organs).

Animals↗
PubMed1982

Chemistry and mutagenicity of alpha-hydroxy nitrosamines.

N-Nitroso-N-(hydroxymethyl)alkylamines, which are key intermediates in the metabolic activation of nitrosamines having a methyl group, were synthesized and their chemical and mutagenic properties were examined. Six N-nitroso-N-(hydroxymethyl)alkylamines (alkyl = methyl, ethyl, n-propyl, n-butyl, sec-butyl, tert-butyl) were prepared by the deoxygenation of N-nitroso-N-(hydroperoxymethyl)alkylamines. Their stability in aqueous solution was highly dependent on pH, being stable in acidic media, but unstable in neutral or alkaline media. The structure also exerted a profound effect on the stability. Thus a branched alkyl group accelerated the decomposition, although compounds with a normal alkyl group showed a similar response to the change of pH. The alkylating activity of the compounds toward deoxyguanosine and thymidine was demonstrated, and was dependent on the reaction solvent used. The overall alkylating activity was found to be highest with the compound ultimately yielding a methylating agent, while a more selective alkylation towards the oxygen, compared to the nitrogen, was observed with the ethylating, propylating and butylating species. Reactions with cysteine and histidine were also observed. A potent mutagenic effect of the N-nitroso-N-(hydroxymethyl)alkylamines was demonstrated in Salmonella typhimurium TA1535 and Escherichia coli WP2 and WP2 hcr-, in the absence of the S9 mix. A good correlation of the activities of the N-nitroso-N-dialkylamines and the N-nitroso-N-(hydroxymethyl)alkylamines with the same alkyl group was demonstrated.

Alkylation↗
PubMed1982

Formation of volatile N-nitrosamines from food products, especially fish, under simulated gastric conditions.

Most food products do not form volatile nitrosamines under the simulated gastric conditions employed in the present study. Fish and other seafood products, however, regularly form nitrosodimethylamine (NDMA), sometimes in amounts of tens of micrograms per 'portion'. These results corroborate the tentative conclusions of a previous report from this laboratory. An attempt has been made to assess the influences of fish species, method of processing (freezing, smoking, canning, marinating, boiling, frying) and degree of freshness, but no particular type of product can be singled out as being a regular source of exceptional NDMA formation. If the model system employed is a valid approximation to the conditions obtaining in the human stomach, these studies suggest that the amounts of NDMA formed in vivo from certain fish samples might far exceed those already present in food products before consumption.

Animals↗
PubMed1982

Mutagenicity of N-alkyl-N-(alpha-hydroperoxyalkyl) nitrosamines in V79 Chinese hamster cells in relation to alkylating activity.

Mutagenicity and cytotoxicity of a series of N-alkyl-N-(alpha-hydroperoxyalkyl)-nitrosamines (alkyl = methyl, ethyl, propyl, butyl and tert-butyl) were tested in V79 Chinese hamster cells to examine the effects of alkyl chain length and the mode of substitution at the alpha-carbon bearing the hydroperoxy group on the biological activities. Among a series of hydroperoxymethyl compounds whose carbon bearing the hydroperoxy group is primary, the N-methyl compound was the most mutagenic and cytotoxic, and the biological activities of the compounds decreased in the following order: methyl much greater than ethyl greater than propyl greater than or equal to butyl greater than tert-butyl, the last one being nonmutagenic at the concentration tested. In a series of alpha-hydroperoxyalkyl compounds whose alpha-carbon bearing the hydroperoxy group is secondary, the N-methyl compound was also found to be the most mutagenic and cytotoxic, and the biological activities of the compounds decreased in the following order: methyl greater than ethyl much greater than propyl greater than butyl. A comparison of the biological activities of the corresponding compounds having the hydroperoxy group at primary or secondary alpha-carbon showed that the latter compounds were far more active than the former. A plot of the alkylating activity of the compounds toward 4-(rho-nitrobenzyl) pyridine after deoxygenation with NaHSO3 versus their mutagenic potency in V79 cells was linear, indicating that the chemical reactivity of the compounds plays an important role in inducing mutation in V79 cells.

Alkylation↗
PubMed1982

Mineral oil vacuum distillation method for nitrosamines in fried bacon, with thermal energy analyzer: collaborative study.

Nine laboratories participated in a collaborative study of a method for determining 6 nitrosamines, dimethylnitrosamine, diethylnitrosamine, dibutylnitrosamine, nitrosopiperidine, nitrosopyrrolidine, and nitrosomorpholine, in the 5-17 ppb range. The coefficients of variation for repeatability were 10.8, 8.5, 10.4, 8.5, 8.7, and 7.8% with corresponding coefficients of variation for reproducibility of 16.4, 12.0, 13.6, 10.8, 11.2, and 10.3% and recoveries of 89.6, 91.6, 84.7, 90.0, 89.6, and 88.1%, respectively. The method was adopted official first action.

Animals↗
PubMed1978

Inhibitory effect of 13-cis-retinoic acid on urinary bladder carcinogenesis induced in C57BL/6 mice by N-butyl-N-(4-hydroxybutyl)-nitrosamine.

The effect of 13-cis-retinoic acid on the induction of urinary bladder carcinoma by N-butyl-N-(4-hydroxybutyl)nitrosamine (OH-BBN) was studied in male C57BL/6 mice. Animals received a total dose of either 90 or 140 mg of OH-BBN via gastric intubations of 7.5 or 10.0 mg of OH-BBN 2 times each week for 6 or 7 weeks, respectively. Seven days after the last OH-BBN intubation, animals were fed laboratory chow diet supplemented with either 200 mg of 13-cis-retinoic acid per kg or its placebo. Animals were killed at 6 months after the first carcinogen intubation. Highly invasive squamous and transitional cell carcinomas of the urothelium were found at autopsy. In the majority of these carcinomas, invasion of the bladder muscle wall by tumor cells had occurred. At the two dose levels of OH-BBN, feeding of 13-cis-retinoic acid reduced the incidence of both carcinomas and noninvasive papillomas, as well as the extent of neoplastic development in the urinary bladder. In mice receiving the lower dose of OH-BBN, the feeding of 13-cis-retinoic acid prevented the appearance of both squamous and transitional cell carcinomas with a reduction in incidence from 33 to 0% (p less than 0.01). The results of this study indicate that 13-cis-retinoic acid reduced not only the severity of highly invasive urinary bladder carcinomas but also the incidence of such cancers.

Animals↗
PubMed1981

Urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl)nitrosamine in dogs.

Clinicopathological, radiological, and histological studies were performed on urinary bladder neoplasia induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in five adult beagle dogs and in ten adult mongrel dogs. Tumors of the urinary bladder developed in dogs given various daily doses of BBN p.o. for different periods. The latent period of tumor induction was 4 years in dogs receiving a daily dose of 80 mg of BBN, 2 to 2.5 years in dogs receiving a daily dose of 160 mg of BBN, and 1.5 years in dogs receiving a daily dose of 240 mg of BBN. The total dose of BBN ingested by the dogs until the first tumors were observed by urological examinations was nearly the same in all groups, 100 to 140 g. These results suggest that there is a correlation between dose and induction time, but further dose-response studies are required. Histologically, tumors of the urinary bladder were transitional cell papillomas or transitional cell carcinomas resembling morphologically those found in human cases. It is possible to observe the process of development of urinary bladder tumors from initial lesions to invasive tumors using routine urological examinations. We believe that this experimental model is valuable for clinicopathological studies of urinary bladder tumors.

Animals↗
PubMed1980

Effect of cyclophosphamide on rat urinary bladder epithelium treated wtih N-butyl-N-(4-hydroxybutyl)nitrosamine.

The effect of cyclophosphamide (CP) on the urinary bladder epithelium of rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was examined histologically to detect preneoplastic papillary or nodular hyperplasia. The urinary bladder epithelium of rats injected intraperitoneally with 40 or 80 mg/kg body weight of CP after treatment with 0.025% BBN for 2 weeks showed extensive epithelial erosion and then simple, or papillary or nodular hyperplasia, but this soon almost disappeared. In contrast, rats given BBN alone showed papillary or nodular hyperplasia later. These findings indicate that epithelial damage by CP inhibited the early neoplastic process of BBN.

Animals↗