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Biomedical subjects

W Lijinsky

Publications and source records attributed to W Lijinsky.

At least 127 records · Page 7Linked to original sources
PubMed1984

Strain and sex differences in N-nitrosohexamethyleneimine carcinogenesis in NZB, NZC, NZO, and NZY mice.

The carcinogenic activity of N-nitrosohexamethyleneimine [(NHEX) CAS: 932-83-2; hexahydro-1-nitroso-1H-azepine] was studied in male and female mice of the four inbred strains NZB/BlGd, NZC/BlGd, NZO/BlGd, and NZY/BlGd. A total of 158 mice received NHEX treatment; 1,338 untreated controls were used, all kept under identical laboratory conditions for their natural life-spans. Beginning at age 50 days a 1.56-mM NHEX solution (200 mg/liter) was given instead of drinking water for 8 weeks, which resulted in nearly the same total dosage of 0.7 +/- 0.04 g or 5.7 +/- 0.2 mmol NHEX/kg body weight in both sexes of all four strains. In both sexes of all four strains the main types of tumors after NHEX treatment were squamous papillomas and carcinomas of the esophagus, squamous stomach, and oropharynx and hepatocellular carcinomas. Tumors of the hepatic bile ducts, glandular stomach, and lung and malignant lymphomas were also induced by NHEX, but these tumors had a predilection for certain strains only. The incidences of other tumors characteristic of the untreated mice in each particular strain, such as tumors of the ovary in NZC, tumors of the breast in NZY, and tumors of the duodenum in NZO, were not increased significantly by NHEX treatment. The incidence of main tumor types in NHEX-treated mice varied greatly between strains, e.g., esophageal papillomas and carcinomas in 81% of male NZC versus 32% in male NZB mice. Some marked sex differences also emerged in NHEX-treated animals, e.g., the occurrence of liver angiosarcomas only in males of three strains and the 53% incidence of hepatocellular tumors in male NZY mice compared to the absence of liver tumors in female NZY mice.

Animals↗
PubMed1984

Comparison of nitrosocimetidine with nitrosomethylnitroguanidine in chronic feeding tests in rats.

N-Nitrosocimetidine, a nitroso derivative of the drug cimetidine, was given to groups of 20 male and 20 female rats in drinking water at a concentration of 0.5 mM for more than 2 years. The life span of the rats was not decreased compared with untreated control animals, and there was no significant increase in incidence of any tumor that could be attributed to the treatment. In comparison, 45% or more of 20 male rats treated with the analogous nitrosoguanidine, N-nitroso-N-methyl-N'-nitroguanidine, at an equimolar concentration in drinking water developed neoplasms of the glandular stomach. There was some shortening of life span in these animals. An additional group of 20 male rats was given an identical treatment with N-nitroso-N-methyl-N'-nitroguanidine in water, but prepared fresh on alternate days, rather than once a week, to minimize decomposition. These animals died more rapidly than did the previous group and had a higher incidence of neoplasms of the glandular stomach. The neoplasms seen in this organ were usually adenomas or adenocarcinomas, but there were a few hemangiosarcomas and neurosarcomas. There is a possibility that nitrosocimetidine could be formed by interaction of cimetidine with nitrite in the stomach, but the carcinogenic risk arising would be very small based on the negative result of this study.

Animals↗
PubMed1983

Chronic toxicity studies of vinyl acetate in Fischer rats.

A chronic toxicity test was carried out in groups of 20 male and female F344 rats with vinyl acetate dissolved in drinking water at two concentrations, 2500 and 1000 mg/liter. Treatment lasted for 2 years and did not lead to early death of the animals compared with untreated controls. The incidence of most types of neoplasm was similar in the treated and control groups. However, six females receiving the higher dose of vinyl acetate had adenoma or carcinoma of the thyroid and five had carcinoma of the uterus; the latter were not seen in the controls.

Animals↗
PubMed1983

Induction of tumors of the esophagus in rats by nitrosomethylalkylamines.

The carcinogenic effectiveness of nitrosomethyl-n-butylamine,-n-hexylamine and -n-heptylamine was compared by administration to F344 rats at various concentrations in drinking water and by gavage in oil. Nitrosomethylbutylamine induced only tumors of the upper gastrointestinal tract, and was very toxic. Nitrosomethylhexylamine was less toxic and induced tumors of the liver and lung, as well as those the upper GI tract, when given by gavage, but only tumors of the GI tract when given in drinking water. In contrast, nitrosomethylheptylamine induced tumors of the liver and lung when given in drinking water or by gavage, but there were tumors of the esophagus only in those rats treated via the drinking water. As measured by the dose needed to produce a given carcinogenic effect, nitrosomethylheptylamine was a weaker carcinogen than the other two nitrosamines, but was not inactive as has been reported previously.

Animals↗
PubMed1983

The superiority of hamster liver microsomal fraction for activating nitrosamines to mutagens in Salmonella typhimurium.

A number of nitrosamines which were carcinogenic in rats were not activated to mutagens in the Salmonella/mammalian microsome assay by the addition of the rat liver microsomal fraction. Some of these nitrosamines induced tumors in the liver of rats and others were carcinogenic to different organs of the rat. Most of these nitrosamines were activated to mutagens by hamster liver microsomal fraction. The use of the hamster preparation showed some compounds to be of very high mutagenic potency. In a few cases the nitrosamines mutagenic with hamster liver activation were more potent carcinogens in the hamster than in the rat. The compounds which were non-mutagenic to Salmonella with either rat or hamster liver activation included the liver carcinogens nitrosomethylethylamine, nitrosodiethanolamine and nitrosoethanolisopropanolamine, the esophageal carcinogens nitrosomethylneopentylamine, nitrosomethylaniline, nitrosomethyl-4-fluoroaniline, nitrosothiomorpholine and nitrosophenylbenzylamine, and the bladder carcinogens nitrosomethyl-3-carboxypropylamine and nitrosodiphenylamine.

Animals↗
PubMed1983

Carcinogenesis by combinations of N-nitroso compounds in rats.

Five N-nitroso compounds were administered individually or in various combinations to groups of 20 female F344 rats to examine possible additive or synergistic effects on mortality rate and the induction of tumours. Combination of the oesophageal carcinogen dinitroso-2,6-dimethylpiperazine with nitrosodiethylamine, which also induces oesophageal tumours, or with nitrosoethylmethylamine, which induces liver tumours, did not appear to increase tumour incidence. Similarly, combination of nitrosodiethylamine with the bladder carcinogen nitrosomethyldodecylamine did not increase the formation of either bladder or oesophageal tumours compared with the effects of either compound alone, although an additive effect was suggested by a higher incidence of liver tumours after the combined treatment than after treatment with either compound alone. Nitrosomethylurethane, which induces tumours of the forestomach in rats, appeared to enhance the effectiveness of nitrosoethylmethylamine and dinitroso-2,6-dimethylpiperazine in inducing tumours of the oesophagus, and increased the rate of death. Nitrosomethylurethane given, at a somewhat higher dose, in combination with both of these compounds increased the incidence of oesophageal tumours even when the treatment lasted only 4 wk. This evidence suggests that additive or synergistic effects of combinations of N-nitroso compounds at low dose rates can be demonstrated in small groups of rats.

Animals↗
PubMed1983

Carcinogenesis in Fischer rats by nitrosodipropylamine, nitrosodibutylamine and nitrosobis(2-oxopropyl)amine given by gavage.

Nitrosodi-n-propylamine, nitrosodi-n-butylamine and the ketone nitrosobis(2-oxopropyl)amine were administered by gavage to F344 rats at doses of 1 and 2 mmol for 30 weeks. The higher level of nitrosodipropylamine led to death of all the animals with carcinomas of the liver, nasal cavity and esophagus by the 40th week. At the lower level the rats died of these tumors but survived to week 60. In contrast, 1 mmol of nitrosobis(2-oxopropyl)amine did not cause death of all the animals until week 95, and fewer than half of them had liver carcinomas; none had tumors of the esophagus or nasal cavity. Nitrosodi-n-butylamine was a much weaker carcinogen than nitrosodipropylamine, since 80% of the rats given 2 mmol survived until week 83. Although, with this compound, the lifespan of the rats was not greatly shortened, a large variety of tumors was induced; about 60% of the animals had liver carcinomas, 50% forestomach carcinomas and 35% transitional cell carcinomas of the urinary bladder.

Animals↗
PubMed1983

Skin carcinogenesis tests in mice of derivatives of 7,12-dimethylbenz[a]anthracene substituted in the 'A' ring.

Seven derivatives of 7,12-dimethylbenz[a]anthracene (DMBA) having substituents in the 'A' ring have been tested for carcinogenic activity by chronic application to the skin of female Swiss mice. Saturation of the A ring, as in 1,2,3,4-tetrahydro-DMBA, resulted in a very potent skin carcinogen which induced almost 100% of skin carcinomas within 26 weeks. The 2-bromo-derivative was apparently not carcinogenic. Respectively, 35% and 40% of the mice treated with 2-methoxy and 4-bromo-DMBA developed skin tumors, mainly squamous cell carcinomas with the former and mainly neurosarcomas for the latter. The remaining compounds, 3-methoxy-, 4-methoxy- and 3-bromo-DMBA each induced skin tumors on 3-5 animals. There were no quantitative correlations between bacterial mutagenicity of the substituted DMBA's and their carcinogenic potencies in mouse skin painting. The reasons for the differences in carcinogenic activity are not clear, but the effects, particularly the strong carcinogenicity of the tetrahydro-derivative, suggest the possibility that mechanisms other than formation of a dihydrodiol expoxide in the A ring might be involved.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

The effect of substituents in the aromatic ring on carcinogenicity of N-nitrosomethylaniline in F344 rats.

N-Nitroso-N-methylaniline (NMA) and N-nitroso-N-methyl-4-fluoroaniline (p-F-NMA), both non-mutagenic in Salmonella typhimurium and N-nitroso-N-methyl-4-nitroaniline (p-NO2-NMA), a potent mutagen, were tested for carcinogenicity in F344 rats. NMA was shown to induce a high level of tumors in the upper gastrointestinal tract, particularly in the esophagus. Male rats treated with NMA died with tumors at a slightly higher rate than females, although the final tumor yield was the same. Most of the rats treated with p-F-NMA also developed tumors of the esophagus, but they died less rapidly than the NMA treated rats, indicating that p-F-NMA is a slightly weaker carcinogen than NMA. The powerful, directly acting mutagen, p-NO2-NMA did not appear to induce tumors at all since its tumor spectrum was essentially identical to that of the untreated control rats. Thus, the carcinogenic activities of NMA and its substituted analogs do not appear to correlate with bacterial mutagenesis assays. Additionally, NMA, p-F-NMA and N-nitroso-N-methyl-4-bromoaniline, the last a strong mutagen in S. typhimurium, were shown not to induce sister chromatid exchanges in CHO cells and in a clone of a CHO:liver cell hybrid which had previously been shown to be sensitive to chemical agents which require metabolic activation.

Aflatoxin B1↗
PubMed1983

Carcinogenicity of methylated nitrosopiperazines in rats and hamsters.

A comparison has been made of the carcinogenic activities of dinitroso-2,6-dimethylpiperazine (Me2DNP) and nitroso-3-4,5-trimethylpiperazine (Me3NP) in F344 rats and Syrian golden hamsters. The compounds were administered in drinking water to the rats and by gavage to the hamsters, at similar dose rates. As measured by the increased rate of mortality from tumors induced, Me2DNP was a more potent carcinogen in rats than Me3NP; Me2DNP induced mainly esophageal tumors, while Me3NP induced tumors of the nasal cavity, but no esophageal tumors. In contrast, in Syrian hamsters, by the same criterion, Me3NP was at least as potent as Me2DNP. Me3NP was more potent in hamsters than Me2DNP as measured by the number and multiplicity of tumors induced. The most numerous tumors induced by both compounds in hamsters were papillomas of the forestomach, but in addition Me3NP induced a high incidence of lung tumors. A small number of hamsters treated with either compound had liver angiosarcomas. Two hamsters given Me3NP had papillomas of the esophagus, a highly unusual tumor in Syrian hamsters.

Animals↗
PubMed1983

Altered incidences of hepatic and hemopoietic neoplasms in F344 rats fed sodium nitrite.

Three groups of 24 male, and three groups of 24 female F344 rats were fed sodium nitrite for 2 years. Two male and two female groups received 2000 parts per million sodium nitrite mixed with powdered food. The remaining pair of groups received 2000 parts per million in drinking water at the rate of 100 ml per week. A similar pair of groups of untreated animals were maintained as controls. There was little difference in survival between the treated groups and the controls. The incidence of liver neoplasms, which were carcinomas and neoplastic nodules, in the two groups of females treated with sodium nitrite in feed was significantly higher than in the controls, but there was no significant difference in the males. The incidence of monocytic leukemia for each of the nitrite-treated groups was always lower than that for the matching untreated control groups, with the difference attaining or approaching significance in five of the six cases.

Animals↗
PubMed1983

Carcinogenesis in F344 rats by N-nitrosomethyl-n-propylamine derivatives.

The carcinogenicity of N-nitrosomethyl-n-propylamine and five of its derivatives, including N-nitrosomethyl-n-butylamine, was compared by oral administration of the compounds to inbred F344 rats. N-Nitromethyl-n-propylamine and N-nitrosomethyl-n-butylamine given in drinking water induced tumors of the upper gastrointestinal tract, mainly carcinomas of the esophagus, and appeared to be of comparable potency. N-Nitrosomethyl(2-hydroxypropyl)amine also mainly induced esophageal carcinomas (100% incidence) and lung tumors, whereas N-nitrosomethyl(2,3-dihydroxypropyl)amine mainly induced nasal cavity tumors and gave rise to a high incidence of esophageal tumors; however, it appeared to be less potent than the monohydroxy compound. N-Nitrosomethyl(2-oxopropyl)amine, the ketone corresponding to N-nitrosomethyl(2-hydroxypropyl)amine, was a more potent carcinogen than the latter at comparable doses in drinking water and gave rise to a high incidence of esophageal tumors and tumors of the trachea; female rats had a high incidence (15/20) of angiosarcomas of the liver, but only 2 male rats died with this tumor. When N-nitrosomethyl(2-oxopropyl)amine was administered at a lower dose in drinking water or at the same dose given by gavage, the incidence of esophageal tumors was lower and there were fewer carcinomas. After administration of large doses in drinking water to male and female rats, N-nitrosomethyl(3-carboxypropyl)amine, a urinary metabolite of several N-nitrosomethyl-n-alkylamines that induce tumors of the urinary bladder in rats, gave rise to a high incidence of transitional cell carcinomas of the bladder. The time to death of animals with these tumors was long, and there were few other tumors.

Administration, Oral↗
PubMed1983

Summation and new approaches to diet and cancer.

Epidemiological studies have shown a relationship between several types of human cancer, such as esophageal, breast, and colon, and particular kinds of diet, indicating the presence of carcinogenic factors in those diets. Observations in animals have shown that some types of cancer in them are related to certain carcinogens in their food. Several types of cancer similar to that in humans have been induced in experimental animals by administration of carcinogens, such as nitrosamines and mycotoxins, suggesting that their presence in human diets can increase cancer risk. The search for such carcinogens, and for others presently unsuspected in human diets, should be continued with the objective of reducing or eliminating human exposure to them. The role of promoting agents, such as fats, in colon and breast cancer needs to be further investigated, and exposure to them should be reduced. Two sources of carcinogens that need increased study are the formation of carcinogens in cooking, especially of fats and proteins, and the endogenous formation of carcinogens in the gastrointestinal tract, e.g., N-nitroso compounds.

Animals↗
PubMed1983

Carcinogenicity of hydroxylated alkylnitrosoureas and of nitrosooxazolidones by mouse skin painting and by gavage in rats.

The carcinogenic effectiveness of a number of nitrosoalkylamides related to nitrosoethylurea and nitroso-n-propylurea has been compared by topical application to Swiss mice and by intragastric administration to F344 rats. Nitrosohydroxyethylurea and the related cyclic nitrosamide, nitrosooxazolidone, were as potent as nitrosoethylurea as skin carcinogens, although the latter was a much weaker mutagen to Salmonella. When administered p.o., nitrosooxazolidone induced mainly forestomach tumors in rats, while nitrosohydroxyethylurea was very broadly acting, inducing neoplasms of the lung, forestomach, glandular stomach, colon, duodenum, and bone (osteogenic sarcomas). Nitroso-2-hydroxypropylurea, nitroso-3-hydroxypropylurea, and nitroso-5-methyloxazolidone were all much more potent carcinogens on mouse skin than was nitroso-n-propylurea, nitroso-5-methyloxazolidone being somewhat less effective than the nitrosoureas; the mutagenicity to Salmonella seemed not to be quantitatively related to carcinogenicity. Nitroso-5-methyloxazolidone given p.o. to rats induced mainly forestomach neoplasms and a few neoplasms of the duodenum, whereas similar treatment of rats with nitroso-2-hydroxypropylurea induced a high incidence of neoplasms of the thymus, some of the forestomach, and few at any other site.

Administration, Topical↗
PubMed1982

Distribution of the liver carcinogen methapyrilene in Fischer rats and its interaction with macromolecules.

The anti-histaminic drug methapyrilene hydrochloride, which induces liver tumors in ras, was labeled with tritium by exchange and administered at a does of 21 mg containing 700 microCi to each of 15 male Fischer rats. At 1 h, 6 h, 14 h, 24 h, and 44 h after treatment three rats were killed and their livers, pancreas, kidneys, and lungs were removed. The pooled organs were homogenized and DNA, RNA, and soluble protein were isolated from each. The extent of interaction of radioactive methapyrilene with liver nucleic acids was exceedingly small and did not differ significantly from the binding to nucleic acids in kidney, lung, or pancreas, which are not target organs of this carcinogen in rats. Binding of radioactivity to soluble proteins of the liver was considerable and substantially greater than in the other organs. If the mechanism of carcinogenic action of methapyrilene involves covalent interaction with DNA this must be at a very low and highly specific level.

Aminopyridines↗