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Biomedical subjects

W Lijinsky

Publications and source records attributed to W Lijinsky.

At least 199 records · Page 11Linked to original sources
PubMed1980

The penetration of rat skin by some nitrosamines of environmental importance.

N-Nitrosomorpholine (NMOR) and N-nitrosodiethanolamine (NDELA) were applied to the clipped dorsal skin (about 3.5 X 3.5 cm) of adult male Fischer 344 rats. NDELA was applied undiluted, dissolved in water and dissolved in cutting oil; NMOR was applied dissolved in water and in ethyl acetate. To compare the extent of absorption through the skin with that from the stomach, aqueous solutions of the nitrosamines were used for gavage. Blood and urine samples were analysed for nitrosamines, using GC-TEA or HPLC-TEA. Maximum skin penetration observed with NMOR was 56%, following application of 5 mg, whereas a similar proportion of the dose was regularly present after gavage of 5 mg. Less than 1% was recovered from the urine. Skin painting of NDELA in water (20 mg in 100 microliter) and in cutting oil (25 mg in 25 microliter) yielded small concentrations of NDELA in the blood; less than 25 mg/l in all cases. However, when 50 mg NDELA was painted on the skin undiluted, from 130 to 220 mg/l of blood were recovered after one hour. fifty mg NDELA in water yielded similar blood concentrations when administered by gavage. From 20 to 30% of the NDELA applied undiluted and by gavage were recovered in the urine. It is concluded that, although there are differences between animals, exposure to NMOR or NDELA represents a risk due to absorption through the skin.

Animals↗
PubMed1980

Carcinogenicity in rats of nitrosomethylethylamines labeled with deuterium in several positions.

Nitrosomethylethylamine and four of its derivatives labeled with deuterium at various positions were administered to male Fischer 344 rats in drinking water at equimolar doses for 30 weeks. The doses were 30 and 6 mg/liter at the rate of 3 and 0.6 mg/week, approximately. The rats receiving the higher doses died earlier and had more tumors than those given the lower doses. At both dose levels, nitrosomethylethyl-1-d2-amine and nitrosomethylethyl-d5-amine were more effective carcinogens than was unsubstituted nitrosomethylethylamine. Rats died earlier and more of them had tumors after receiving the deuterium-labeled compounds. Nitrosomethyl-d3-ethylamine and nitrosomethyl-d3-ethyl-d5-amine did not greatly differ in carcinogenic effectiveness from the unsubstituted compound. Both nitrosamines having deuterium in the methyl portion of the ethyl group, nitrosomethylethul-d5-amine and nitrosomethyl-d3-ethyl-d5-amine, induced esophageal tumors as well as liver tumors in the rats.

Animals↗
PubMed1980

Comparison of the carcinogenic effects of five nitrosamines in guinea pigs.

Five nitrosamines which were potent carcinogens in rats or hamsters were administered by gavage in olive oil solution twice a week to 20 male strain 2 guinea pigs. Nitroso-2,6-dimethylmorpholine given at 80 mg/kg/week for 12 weeks or at 32 mg/kg/week for 35 weeks gave rise to hemangioendothelial sarcomas of the liver in 6 and 19 animals, respectively. The same tumors were induced in 18 animals by dinitroso-2,6,dimethylpiperazine, together with hepatocellular carcinomas in six animals. Nitrosomethyldodecylamine also induced mainly hemangioendothelial sarcomas of the liver (12 animals). A few bile duct carcinomas were also observed. Neither nitrosoheptamethyleneimine nor nitrosomethyldiethylurea seemed to induce tumors in guinea pigs under our conditions.

Animals↗
PubMed1980

Carcinogenicity of 3-chloronitrosopiperidine, 4-chloronitrosopiperidine, and 3,4-dichloronitrosopiperidine in Fischer rats.

Three chlorinated nitrosopiperidines, 3-chloro-, 4-chloro-, and 3,4-dichloronitrosopiperidine, were administered to groups of 20 male Fischer 344 rats at a concentration of 0.17 mM in drinking water. Treatment with the monochloro compounds lasted for 30 weeks, while treatment with the dichloro compound lasted for 21 weeks. Almost all of the animals died with esophageal tumors. There was also a significant incidence of tumors of the forestomach and tongue in the rats treated with the monochloro compounds. Using the rate of death of the animals with tumors as an index, the relative potency of the three compounds increases from 3-chloro- to 4-chloro- to 3,4-dichloronitrosopiperidine.

Animals↗
PubMed1979

Carcinogenicity of chlorinated nitrosotrialkylureas in rats.

Four chlorinated derivatives of nitrosotrialkylureas were tested for carcinogenicity by oral administration by gavage to Sprague-Dawley rats. All of the compounds were very toxic, and all were carcinogenic, inducing tumors of the non-glandular stomach and of the lungs. The commonest tumors were carcinomas and papillomas of the non-glandular stomach and alveolar cell adenomas of the lungs. Nitrosochloroethyldimethylurea induced most tumors, but it was possible to administer higher doses of this compound than of the others, which were nitrosochloroethydiethylurea, nitrosomethylbis-(chloroethyl)-urea and nitrosotris-(chloroethyl)-urea. The last of these was a particularly toxic compound so that the maximum total dose given was only 0.07 millimole per rat.

Animals↗
PubMed1979

Mutagenicity of aliphatic nitrosamines in Salmonella typhimurium.

25 aliphatic nitrosamines were examined in the Ames assay for bacterial mutagens, using rat liver "S-9" for activation. Of them, 8 carcinogens were mutagenic and 5 non-carcinogens were not mutagenic. However, 2 compounds not carcinogenic in rats were mutagenic and 9 carcinogens were not mutagenic, including 6 that are liver carcinogens in rats.

Carcinogens↗
PubMed1979

The mutagenicity of nitrosamides in Salmonella typhimurium.

34 nitrosamides (10 nitrosoalkylcarbamates, 2 nitrosoalkylnitroguanidines, 12 nitrosoalkylureas, 6 substituted nitrosoalkylureas, and 4 cyclic nitrosoalkylureas) were tested for mutagenicity in Salmonella. All were direct-acting mutagens of varying potency.

Carcinogens↗
PubMed1979

Mutagenicity of cyclic nitrosamines in Salmonella typhimurium: effect of ring size.

Mutagenicity of cyclic nitrosamines with varying carcinogenic potentials was assayed in the Salmonella histidine-reversion system. Mutagenicity in the pour-plate assay was compared with that in the liquid pre-incubation test. The smaller ring compounds (nitrosoazetidine, nitrosopyrrolidine, and nitrosopiperidine) exhibited a similar effect in both assays. The large ring compounds (nitrosohexamethyleneimine, nitrosoheptamethyleneimine, nitrosooctamethyleneimine, and nitrosododecamethyleneimine) were more effective in the liquid pre-incubation test. Our results suggest a reasonable relationship between their mutagenic and carcinogenic activities.

Drug Evaluation, Preclinical↗
PubMed1979

Effects of N-nitrosopiperidine substitutions on mutagenicity in Drosophila melanogaster.

N-Nitrosopiperidine (NP) and various derivatives were fed to Drosophila melanogaster males over a wide concentration range in order to assess their mutagenic potency in the induction of X-linked recessive lethals and chromosome loss. NP was effective in inducing lethals, as were its halogen and methyl-substituted derivatives, with the exception of 2,6-dimethyl NP. (Methyl substitutions at the alpha carbon atoms reduce or eliminate mutagenic activity.) Substitution of halogen groups on the piperidine ring enhanced the mutagenic activity, with the 3-chloro compound being the most mutagenic. In contrast, substitutions with a hydroxyl, carboxyl, or keto group resulted in a loss of mutagenicity. None of the compounds tested increased the frequency of chromosome loss or breakage in mature sperm.

Animals↗
PubMed1979

Mutagenicity of nitrosamines formed from nitrosation of spermidine.

5 nitrosamines formed from the nitrosation of spermidine were investigated for mutagenicity using various strains of Salmonella typhimurium in the presence and absence of S9 mix. Using the plate incorporation method, 3-butenyl-(2-propenyl)-N-nitrosamine, 3-hydroxybutyl (2-hydroxypropyl)-N-nitrosamine, 4-hyroxybutyl-(2-hydroxypropyl)-N-nitrosamine, 4 hydroxybutyl-(3-hydroxypropyl)-N-nitrosamine, and in the liquid test 3-hydroxybutyl-(3-hydroxypropyl)-N-nitrosamine were mutagenic in the absence of S9 mix.

Dose-Response Relationship, Drug↗
PubMed1979

Relative extents of hydrogen-deuterium exchange of nitrosamines: relevance to biological isotope effect studies.

Relative extents of base-catalyzed, hydrogen-deuterium exchange have been determined for a number of nitrosamines. Observed trends in the exchanges are discussed in terms of substitution, ring size and conformation. The relevance of the exchanges to deuterium isotope effects in carcinogenesis tests is discussed. Those compounds which give pronounced biological isotope effects undergo exchange only to a small extent. No biological isotope effect is found for compounds which undergo extensive exchange.

Animals↗
PubMed1979

Carcinogenicity of methylated derivatives of N-nitrosodiethylamine and related compounds in Sprague-Dawley rats.

Five nitrosamines, which can be considered alkyl derivatives of N-nitrosodiethylamine, were tested for carcinogenicity by administration to Sprague-Dawley rats in drinking water at approximately equimolar concentrations. N-Nitrosodi-n-propylamine was a potent carcinogen but less so than N-nitrosodiethylamine and gave the same spectrum of tumors. N-Nitrosodiisopropylamine was very much weaker than N-nitrosodiethylamine and induced only tumors of the nasal turbinates in significant incidence. At the doses given, neither N-nitrosodiisobutylamine nor N-nitrosodi-sec-butylamine was significantly carcinogenic. In contrast, the cyclic nitrosamine N-nitrosohexamethyleneimine was equally potent with N-nitrosodiethylamine and gave the same spectrum of tumors in liver, esophagus, and nasal turbinates. The results support the concept that oxidation at the alpha carbon atom of nitrosamines is a significant step in carcinogenesis.

Animals↗
PubMed1979

Current status of experimental chemical carcinogenesis and its applications to human cancer risk.

The history of chemical carcinogenesis is a record of the observations of physicians and epidemiologists of the relation between the occurrence of uncommon cancers in humans and the exposures of those people to certain chemical agents. In parallel with some of these findings, experimental animal models were developed to imitate the findings in humans. From these experimental studies has been obtained most of the information we have about the mechanisms of chemical carcinogenesis. Many of the biochemical studies have focused on liver cancer which might be an inappropriate general model for chemically induced cancer, liver cancer being comparatively rare in humans. It is not known to what extent exposures to any particular chemical carcinogens are responsible for the major human cancers, and the agents responsible for most of them are not known. It is probable that many noncarcinogenic chemicals act as promotors of carcinogenesis, and among these alcohol can be included as in important contributor.

Alcoholism↗
PubMed1979

In vivo autoradiography and nitrosoheptamethyleneimine carcinogenesis in hamsters.

Quantitative autoradiograms were made, in vivo, in European hamsters with the use of [14C]nitrosoheptamethyleneimine (260 muCi/animal; time between administration of nitrosamine and killing of animals, 6 hr). In this species, the lung is the principal target, and radioactivity was found in the Clara cells of the bronchial epithelium and in the nitrosoheptamethyleneimine-induced tumors which derive from these cells. Tumors are not induced in the liver, which can metabolize this compound, and labeling is found principally in the cytoplasm, whereas in the target cells there is a high degree of labeling in both the cytoplasm and the nuclei.

Animals↗
PubMed1978

The change in carcinogenic effectiveness of some cyclic nitrosamines at different doses.

The carcinogenic effectiveness in rats of three cyclic nitrosamines administered at two doses separated by a factor of five has been studied. All three compounds showed a response at the lower dose quite different from that at the higher dose. One, 2,6-dimethyl-dinitrosopiperazine, was only a little less effective at the lower dose than at the higher dose, giving 100% nasal turbinate tumors, but only 33% esophageal tumors, compared with 100% esophageal tumors at the higher dose. 3,4-Dichloronitrosopiperidine gave 100% incidence of esophageal tumors at the higher dose. At the lower dose, survival of the rats was very much better, some living 80 weeks, and, in addition to the esophagus, there were tumors of several organs including forestomach, tongue, and nasal turbinates. On the other hand, 2,6-dimethylnitrosomorpholine was a very much weaker carcinogen at the lower than at the higher dose, only six animals dying with tumors, compared with 100% incidence at the higher dose. However, the pattern of mortality of rats given the lower dose of dimethylnitrosomorpholine was similar to that of rats given the lower dose of dichloronitrosopiperidine.

Animals↗