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Biomedical subjects

W Lijinsky

Publications and source records attributed to W Lijinsky.

At least 235 records · Page 13Linked to original sources
PubMed1977

Carcinogenesis tests of nitroso-N-methylpiperazine, 2,3,5,6-tetramethyldinitrosopiperazine, nitrosoisonipecotic acid and nitrosomethoxymethylamine in rats.

Four nitrosamines; nitroso-N-methylpiperazine, 2,3,5,6-tetramethyldinitrosopiperazine, nitrosoisonipecotic acid and nitrosomethoxymethylamine, closely related in structure to potent carcinogens, were fed chronically to rats in drinking water for one year. No toxic effects leading to life shortening were observed. There was no significant incidence of any malignant tumor other than the endocrine tumors normally found in untreated animals of our colony. This indicated that the small changes in structure represented by these compounds were sufficient to reduce greatly, or eliminate, the carcinogenic action.

Adrenal Gland Neoplasms↗
PubMed1977

Chronic oral administration of 1-nitrosopiperazine at high doses to MRC rats.

1-Nitrosopiperazine was fed to two groups of rats as drinking water solutions containing 400 mg/liter (3.5 millimolar) and 800 mg/liter (7.0 millimolar), respectively. The treatment was 20 ml per rat per day, 5 days per week for life. In both groups many animals died with olfactory tumors (mostly esthesioneuroblastomas), the first at 36 weeks in the higher dose group, the first at 64 weeks in the lower dose group. There was also a small number of liver tumors in both groups. None of these tumors was seen in the untreated controls. The similarity of this tumor distribution to that produced by 1,4-dinitrosopiperazine suggests that the observed carcinogenicity of 1-nitrosopiperazine may be entirely due to its disproportionation in the acidic medium of the rat stomach. Chemical data supporting this interpretation are presented.

Administration, Oral↗
PubMed1977

Nitrosamines and nitrosamides in the etiology of gastrointestinal cancer.

It has been amply demonstrated that N-nitroso compounds are formed by interaction of nitrite with secondary and tertiary amino compounds, and that this reaction can occur in vivo as well as in food processed with nitrite. The favored site of reaction in vivo is the stomach. It is likely that N-nitroso compounds formed in this way, especially nitrosamides, could reach the colon and contribute to the induction of colon tumors.

Amides↗
PubMed1977

Liposolubility as an aspect of nitrosamine carcinogenicity: quantitative correlations and qualitative observations.

Carcinogenicity data for a number of nitrosamines have been examined for possible structure-activity correlations with liposolubility by the method of Hansch. Correlations were found in two cases which support a previous mechanistic suggestion and which also suggest a possible difference between the action of nitrosopiperidines and dinitrosopiperazines in inducing olfactory carcinomas. No correlations were found for non-cyclic nitrosamines.

Alcohols↗
PubMed1977

Induction of pancreatic duct of carcinomas in the Syrian hamster with 2,6-dimethylnitrosomorpholine.

Pancreatic duct carcinomas were induced in Syrian hamsters by intragastric administration of 2,6-dimethylnitrosomorpholine. As early as 30 weeks after treatment began, tumors were macroscopically visible in the pancreas; the maximum incidence of such tumors reached 71% by the end of the experiment. They were ductal in origin, and some metastasized to the lung. They were identified histologically as adenomas and carcinomas and developed in different parts of the organ without demonstrating any preferred localization.

Animals↗
PubMed1977

Metabolism of three cyclic nitrosamines in Sprague-Dawley rats.

The metabolism of three cyclic nitrosamines has been studied in Sprague-Dawley rats. The compounds were nitrosopyrrolidine, nitrosohexamethyleneimine, and nitrosohepatamethyleneimine and were labeled at the alpha carbon with 14C. At low doses (2 to 4 mg/animal) the compounds were metabolized to 14CO2 to the extent of 77, 43, and 27%, respectively, after 24 hr. At doses closer to the 50% lethal dose of the compounds (70 to 160 mg/animal) the metabolism values were only 14, 4, and 8%, respectively, after 24 hr. The significance of these results is discussed.

Air↗
PubMed1976

Nitrosocarbaryl: its effect on human DNA.

Human skin cells (both normal and xeroderma pigmentosum) were treated with carbaryl (N-methyl-1-naphthyl-carbamate), a common agricultural pesticide, or its N-nitroso derivative, nitrosocarbaryl, and the DNA of the cells was sedimented in alkaline sucrose gradients at several times after treatment. Numerous single-strand breaks were apparent in the DNA of the nitrosocarbaryl-treated cells but not in the DNA of those treated with carbaryl. The nitrosocarbaryl effect on the DNA could be observed up to 20 h after removal of the chemical from the cultures. The DNA of human cells treated with ring labeled nitroso[3H]carbaryl and methyl labeled nitroso[14C]carbaryl was isolated and banded in cesium chloride density gradients. The peak of 14C radioactivity and not the 3H radioactivity coincided with the optical density peak of the human DNA from these gradients. An aliquot of the same DNA was alkaline denatured and banded on alkaline cesium chloride gradients with similar results. These observations suggest that the nitrosocarbaryl molecule is split and only the methyl containing residue forms an irreversible association with human cellular DNA, resulting in chemical changes observable as alkali-sensitive bonds.

Carbaryl↗
PubMed1976

Reduction of rat liver carcinogenicity of 4-nitrosomorpholine by alpha-deuterium substitution.

Groups of 30 males Sprague-Dawley rats were given 4-nitrosomorpholine-3,3,5,5-d in their drinking water at concentrations of 0.35 and 0.07 X 10(-3) M for 30 weeks. Two similar groups of rats were simultaneously given unlabeled 4-nitrosomorpholine (NM) at the same malar concentrations; all animals were observed throughout their lives. Those receiving the alpha-deuterium-labeled compound had significantly fewer liver tumors than did the corresponding animals receiving the unlabeled compound. The difference in potency appeared to be at least fivefold, a magnitude consistent with a primary kinetic isotope effect on the carcinogenic action of NM. Thus breakage of a bond linking a hydrogen (deuterium) atom with carbon adjacent to the nitrosamino function may be involved in a rate-limiting step of carcinogenesis by NM.

Animals↗
PubMed1976

Carcinogenicity test of two unstaurated derivatives of N-nitrosopiperdine in Sprague-Dawley rats.

Two unsaturated derivatives of N-nitrosopiperidine (NP), N-nitroso-1,2,3,6-tetrahydropyridine (NTP) and N-nitrosoguvacoline (NGC), were administered to Sprague-Dawley rats as solutions in drinking water at concentrations equimolar (0.88X10(-3) M) with those used to test NP. NTP gave rise to hepatocellular tumors in contrast to the esophageal or olfactory tumors that were induced by NP. NGS did not induce tumors under these test conditions.

Animals↗
PubMed1976

Oncogenicity tests of p-nitroso-N,N-dimethylaniline and p-nitroso-N,N-diethylaniline in NZR rats and NZO mice.

Whole-of-life tests of the C-nitroso compounds p-nitrosodimethylaniline (NDMA) and p-nitroso-diethylaniline (NDEA) have been completed in male rats and mice fed maximum tolerated doses continuously over the first halves of their respective natural lifespans. The chemicals were offered at a concentration of 300 mg/litre drinking fluid, but the doses of NDEA consumed were only 75% of the NDMA doses, in both species. Possibly because of this the results with NDEA were statistically not clear-cut, but there was a significant increase in tumour incidence after NDMA treatment in both species. The main sites of tumorigenesis after NDMA were lung, kidney and malignant lymphoma in the rats, and lung, duodenum and malignant lymphoma in the mice. The results confirm our own earlier experiment and provide the first evidence of oncogenic activity in this class of compounds.

Adenocarcinoma↗
PubMed1976

The effect of substituents on the carcinogenicity of n-nitrosopyrrolidine in Sprague-Dawley rats.

N-Nitrosopyrrolidine and two of its derivatives were prepared and fed in drinking water to Sprague-Dawley rats to compare the effects of substituents on the carcinogenicity of the N-nitrosopyrrolidine molecule. 3,4-Dichloro-N-nitrosopyrrolidine induced esophageal tumors in 13 of 14 animals, olfactory carcinomas in 4, and a hepatocellular tumor in 1. All animals that received this compound were dead at 55 weeks after the start of the experiments. N-Nitrosopyrrolidine induced hepatocellular tumors in 26 of 29 animals and induced 1 olfactory carcinoma. Not all animals in this group were dead until 104 weeks of the experiment. 2,5-Dimethyl-N-nitrosopyrrolidine induced only 2 hepatocellular tumors in 29 animals. The alpha-methyl substitution diminished the liver carcinogenicity, while the beta chlorine substitution affected a different target organ, the esophagus, and greatly reduced the time to death with tumors.

Animals↗
PubMed1976

Mutagenicity of cyclic nitrosamines in Escherichia coli following activation with rat liver microsomes.

Ten cyclic nitrosamines were tested for mutagenicity in Escherichia coli after incubation in vitro with 9000 X g microsomal supernatants prepared from rat liver, and the results were compared with carcinogenicity data from the same species. None of the compounds was mutagenic in the absence of microsomes. Seven carcinogenic compounds, nitrosopyrrolidine, nitrosopiperidine, nitrosohexamethyleneimine, nitrosoheptamethyleneimine, nitrosomorpholine, dinitrosopiperazine, and dinitrosohomopiperzine, were mutagenic after microsomal activation. One compound, nitrosohepamethyleneimine, was toxic to the bacteria. Two noncarcinogens, 1-nitrosopiperazine and 1-methyl-4-nitrosopiperazine, and 1 strong carcinogen, 2,6-dimethyldinitrosopiperazine, were not mutagenic with or without microsomal incubation. The liver microsome preparation activated equally well those compounds that are liver carcinogens in Sprague-Dawley rats, and compounds for which the liver is not a target organ.

Animals↗
PubMed1976

Carcinogenesis in Sprague-Dawley rats of N-nitroso-N-alkylcarbamate esters.

Nitrosocarbaryl, nitroso-N-methylurethane and nitroso-N-ethylurethane were administered by gavage in olive oil solution to groups of 12 female Sprague-Dawley rats. The dose was 0.2 ml of 0.11 M solution once a week for 10 weeks, a total dose of 0.22 mmol. The rats given nitrosocarbaryl survived longer, but had as high an incidence of tumors (75%) as did rats given nitrosomethylurethane. Most of the tumors induced were invasive squamous carcinomas of the stomach. Nitrosoethylurethane appeared to be a little more potent than nitrosomethylurethane; all 12 animals in this group had squamous stomach tumors at death. A higher total dose of nitrosocarbaryl, 1.3 mmol, given to male rats twice weekly for 20 weeks did not produce a higher incidence of stomach tumors than did thelower dose in females, although the males died earlier with tumors.

Administration, Oral↗
PubMed1975

Tumor induction in rats by feeding aminopyrine or oxytetracycline with nitrite.

Sprague-Dawley rats were given combinations of aminopyrine or oxytetracycline and sodium nitrite in drinking water. Of 30 animals receiving 0.1% (1,000 ppm) of aminopyrine and sodium nitrite for 30 weeks, 29 died with hemangioendothelial sarcomas of the liver. The same tumor caused death in 26 of 30 animals that received 0.025% (250 ppm) of both aminopyrine and sodium nitrite for 50 weeks. No animals in a control group of the same size that received 0.1% aminopyrine for 30 weeks developed this tumor, although one-half of them were still alive 2 years after the experiment was begun. After feeding a comparable dose (0.1%) of oxytetracycline and sodium nitrite for 60 weeks, liver tumors were present in 4 of 30 rats (3 hepatocellular tumors and 1 cholangioma). Since aminopyrine has been widely used for medicinal purposes in the human population, it is possible that many people have been exposed to a potent carcinogen (dimethylnitrosamine) by its formation in vivo. It is not certain whether the result of feeding oxytetracycline and sodium nitrite indicates significant carcinogenicity of this combination.

Adenoma, Bile Duct↗