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.

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.

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.

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.

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.

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.

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 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.

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.

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.

Carcinogenicity of N-nitroso-3,4-dichloro- and n-nitroso-3,4-dibromopiperidine in rats.

The carcinogenic potencies of 3,4-dichloro- and 3,4-dibromonitrosopiperdine were compared with that of nitrosopiperidine by feeding to groups of 15 male rats in drinking water. A treatment of 15 weeks with a total of 0.5 mmole of the dichloro compound led to death of all animals before 24 weeks with tumors of the tongue, pharynx, esophagus, nonglandular stomach, nasal turbinates, trachea, bronchi, and bronchioles.

Tumorigenesis by oxygenated nitrosopiperidines in rats.

Three oxygenated N-nitrosopiperidines--nitroso-3-piperidinol, nitroso-4-piperidinol, and nitroso-4-piperidone--were prepared and given in drinking water at equivalent molar doses to Sprague-Dawley rats. All were potent carcinogens, 100% of the rats developed tumors in all treatment groups. Nitroso-3-piperidinol resembled nitrosopiperidine in inducing a high incidence of tumors of the nasal cavity and upper alimentary tract, and a few liver tumors.

Carcinogenicity of methylated nitrosopiperidines.

The carcinogenicity of nitrosopiperidine and five methylated derivatives was compared by feeding them to rats at equimolar concentrations in drinking water, at the rate of 20 ml per day, 5 days a week. The maximum treatment time was 50 weeks. Nitrosopiperidine, 2-methyl-, 3-methyl- and 4-methyl-nitrosopiperidine induced tumors of the nasal turbinates or upper gastrointestinal tract in almost 100% of the animals.

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.

Induction of neurogenic tumors by nitrosotrialkylureas in rats.

Four nitrosotrialkylureas were each fed to groups of 15 male and 15 female Sprague-Dawley rats for 50 weeks in drinking water at the same molar concentration. Tumors of nervous origin arose after treatment with nitrosotrimethylurea (3/30), notrosotriethylurea (7/30), nitrosomethyldiethylurea (23/30), and nitrosoethyldimethylurea (8/30). A comparison of the relative stabilities of the four nitrosoureas in aqueous solution at various pH's showed no correlation with the tumorigenicities of the compounds.

Increased carcinogenicity of 2,6-dimethylnitrosomopholine compared with nitrosomopholine in rats.

Nitrosomorpholine was given to rats in drinking water at the rate of 4 mg/week for 30 weeks. Tumors of the liver were induced in 53% of treated animals and were of both hepatocellular and Kupffer cell origin. One-half of the treated animals were alive 75 weeks after the beginning of treatment, but only 2 survived to 104 weeks.

Induction of urinary bladder tumors in rats by administration nitrosomethyldodecylamine.

Nitrosomethyl-n-dodecylamine, a product of the reaction of dimethyl-n-dodecylamine with nitrous acid, was given to Sprague-Dawley rats by gavage in olive oil solution. Twice-weekly treatments with 12 mg of the nitrosamine for 50 weeks gave rise to 100% incidence of transitional cell carcinomas of the urinary bladder. In contrast with the tests of other N-nitroso compounds, this compound seemed to be more effective in males than in females; females died later with the tumor although the dose per unit body weight was higher in females than in males.

Tumor induction in rats by feeding heptamethyleneimine and nitrite in water.

Groups of 15 males and 15 females Sprague-Dawley rats were given 20 ml of drinking water solution containing either 0.2% heptamethyleneimine hydrochloride or this salt together with 0.2% sodium nitrite, 5 days a week for 28 weeks.