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Biomedical subjects

W Lijinsky

Publications and source records attributed to W Lijinsky.

At least 217 records · Page 12Linked to original sources
PubMed1978

Carcinogenicity of 4-chloronitrosopiperidine in Sprague-Dawley rats.

4-Chloronitrosopiperidine was administered to a group of 15 male Sprague-Dawley rats as a 0.005% solution in drinking water for 27 weeks. Of the 15 animals, 12 died with tumors induced by the treatment, half of them by the 41 st week; all 15 were dead at 58 weeks. Seven rats had liver tumors, 5 had esophageal tumors, 2 had tumors of the nonglandular stomach and 2 had tumors of the nasal turbinates. Several rats had tumors of more than one organ.

Animals↗
PubMed1978

Mass spectrometry of N-nitrosamines.

The preparation of a series of N-nitrosamines for carcinogenicity studies presented an opportunity to study mass spectral fragmentation schemes in detail. Condensed spectra are listed for 146 N-nitrosamines of widely differing structures, including nitroso derivatives of commercial drugs and insecticides. Aliphatic nitrosamines were generally characterized by molecular ions and loss of OH. Subsequent fragmentation via alpha-cleavage is similar to that of aliphatic amines. The loss of OH is believed to result in a cyclic ion. Subsituted aliphatic nitrosamines varied in fragmentation schemes with structure and position of the substitutent groups. However, most showed alpha-cleavage at some point in fragmentation. When substituted with aromatic groups prominent peaks due to the aromatic moiety were observed. The alicyclic nitrosamines showed losses of NO, NOH and OH and subsequent alpha-cleavages. Nitrosamides were characterized by rupture of the carbonyl to nitrogen bond. Spectra of substituted ureas usually showed charge retention by the carbonyl fragment, while carbamate esters showed ions from both fragments.

Carcinogens↗
PubMed1978

Mutagenicity of N-nitrosopiperazine derivatives in Salmonella typhimurium.

Mutagenicity of several nitroso derivatives of piperazine was assayed using histidine auxotrophic strains of Salmonella typhimurium. Nitroso derivatives of piperazine required metabolic activation with preference to phenobarbital induced rat-liver microsomal enzymes. We observed a good correlation between a positive effect in the mutation assay and the carcinogenic potency of the compound. Even though our results are not in complete agreement with earlier published work using several microbial mutation assay systems, the differences we observed demonstrate the predictive value of an in vitro activation system using S. typhimurium to detect carcinogenic compounds as mutagens.

Animals↗
PubMed1978

Mutagenicity of methylated N-nitrosopiperidines in Saccharomyces cerevisiae.

N-Nitrosopiperidine (NP) and a number of methylated derivatives were examined for mutagenicity in Saccharomyces cerevisiae. NP, 2-methyl-NP, 3-methyl-NP, 4-methyl-NP and 3,5-dimethyl-NP were mutagens when metabolic activation (rat-liver microsomes) was provided. 2,6-Dimethyl-NP was not a mutagen. The NPs giving a positive response stimulated forward mutation to canavanine resistance (CAN1 leads to can1) and reversion of the his1-7 missense marker. Neither locus revertants nor suppressors of the lys1-1 ochre marker were induced, nor were revertants of the putative frameshift hom3-10.

Animals↗
PubMed1978

Carcinogenesis of nitrosomethylundecylamine in Fischer rats.

Nitrosomethylundecylamine was synthesized and administered to Fischer rats by gavage in olive oil solution, at a dose of 46 mg/animal/week for 30 weeks. There were high incidences of hepatocellular carcinomas and cholangiocarcinomas in the liver and of squamous cell carcinomas and alveolar cell adenocarcinomas in the lung. In contrast with the activity of the next higher homolog, nitrosomethyldodecylamine, no bladder tumors were induced.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1978

Comparison of bladder carcinogenesis by nitrosomethyldodecylamine in Sprague--Dawley and Fischer rats carrying transplanted bladder tissue.

Nitrosomethyldodecylamine was given by gavage in oliver oil solution (25 mg twice/week) to male and female Sprague--Dawley and Fischer rats to the back of each of which had been transplanted a suspension of urinary bladder tissue from the same strain. While there was 100% incidence of transitional cell carcinomas in the host urinary bladders, and few other tumors in the animals, there was a tumor in only 1 transplant in a Sprague--Dawley rat, with a possible tumor in another, and none in the Fischer rat, although these were inbred. In a significant number of cases the transplant survived.

Animals↗
PubMed1978

Carcinogenic effect of N-nitroso-2,6-dimethylmorpholine in Syrian golden hamsters.

N-Nitroso-2,6-dimethylmorpholine was intragastrically administered to Syrian golden hamsters at four different dose levels [74 mg/kg body wt = 1/5 median lethal dose (LD50); 37 mg/kg body wt = 1/10 LD50; 18 mg/kg body wt = 1/20 LD50; and 9 mg/kg body wt = 1/40 LD50]. Up to a 71% rate of pancreatic tumors was induced. These tumors were adenomas or adenocarcinomas of ductal origin. In addition, neoplasms developed in different percentages in the nasal cavities, larynx, trachea, lungs, liver, gallbladder, kidneys, and forestomach. The number of tumors induced was not significantly dose-dependent.

Animals↗
PubMed1978

Carcinogenicity of subcutaneously injected N-nitrosoheptamethyleneimine in European hamsters.

Male and female European hamsters (45 of each sex) recieved sc injections once weekly for life of N-nitrosoheptamethyleneimine (NHMI) at one-fifth the median lethal dose (LD50) (females: 44 mg/kg body wt; males: 66 mg/kg body wt), one-tenth the LD50 (females: 22 mg/kg body wt; males: 33 mg/kg body wt), or one-twentieth the LD50 (females: 11 mg/kg body wt; males: 16.5 mg/kg body wt). Survival times for both males and females were dependent on the dose of NHMI. Pulmonary neoplasms were induced in almost all the treated animals. They were histologically diagnosed as adenocarcinomas, squamous cell carcinomas, and mixed cell carcinomas. In addition, nasal cavity tumors developed in all hamsters of all treatment groups; these were papillomas, squamous cell carcinomas, and a few adenocarcinomas. Only 1 tumor of the larynx and 1 tumor of the trachea were observed. Several papillomas and a few carcinomas were also detected in the forestomach. The results were discussed with reference to previous findings in rats and Syrian golden hamsters.

Adenocarcinoma↗
PubMed1978

Relative carcinogenic effectiveness of derivatives of nitrosodiethylamine in rats.

The carcinogenicity of five derivatives of nitrosodiethylamine was compared with that of the parent compound by p.o. administration to rats. All were less potent than was nitrosodiethylamine. When nitrosobis(2-methoxyethyl)amine and nitrosobis(2-ethoxyethyl)amine were administered at equimolar doses in drinking water, there was a high incidence of liver tumors, but the animals died later than they did after nitrosodiethylamine treatment, which also induced esophageal tumors. Nitrosoiminodipropionitrile and nitrosobis(2,2-diethoxyethyl)amine failed to induce tumors at the same dose level. Nitrosobis(2-chloroethyl)amine was administered in oil by gavage at a dose lower than that of nitrosodiethylamine and produced a much weaker tumor response; 5 of 15 treated rats had forestomach papillomas, and 1 had olfactory adenocarcinoma and no other induced tumors.

Administration, Oral↗
PubMed1977

Urinary bladder neoplasms in Syrian hamsters after administration of N-nitroso-N-methyl-N-dodecylamine.

The biological effect of N-nitroso-N-methyl-N-dodecylamine (NMDA) was examined in Syrian hamsters as part of a comparative study. Data obtained show that after intragastric administration of NMDA, the urinary bladder was the main target organ for the carcinogenic effect. Transitional cell neoplasms developed and a positive dose response relationship was observed. Lung tumors occurred only in female hamsters, whereas males more frequently showed neoplasms of the nasal cavity and digestive tract.

Amines↗
PubMed1977

Carcinogenicity of nitrosoazetidine and tetradeuteronitrosoazetidine in Sprague-Dawley Rats.

Nitrosoazetidine was fed to rats in drinking water at three different concentrations. At 2 mmol (10 mmol total dose) all of the rats died with hepatocellular carcinomas by the 62nd week. This was a greater response than to an equivalent dose of nitrosopyrrolidine. At 0.67 mmol, 6 of 21 rats developed liver tumors, and at 0.17 millimolar 2 of 30 animals had liver tumors. The comparable responses to feeding of nitrosoazetidine-2,2,4,4-d4 were 3 of 21 rats with liver tumors at 0.69 millimolar and 3 of 30 rats with liver tumors at 0.17 mmol. These results show only a small deuterium isotope effect in liver carcinogenesis with nitrosoazetidine.

Animals↗