PubMed Health⌕ Search

Biomedical subjects

M D Reuber

Publications and source records attributed to M D Reuber.

At least 55 records · Page 3Linked to original sources
PubMed1981

Comparative carcinogenicity of two isomers of nitroso-2,6-dimethylmorpholine in guinea pigs.

The cis and trans isomers of nitroso-2,6-dimethylmorpholine (Me2NMOR) were administered by gavage to male Strain-2 guinea pigs as solutions in oil twice weekly for 30 weeks. Those animals treated with the cis isomer developed almost 100% incidence of liver tumors, together with tumors of the lung and adrenal cortex. In contrast, almost none of the animals treated with the trans isomer died with tumors. In rats, the trans isomer was considerably more potent than the cis, whereas this is not the result in guinea pigs, in which the cis is possibly more potent than the trans. This suggests that the mechanisms of activation in the 2 species might be different.

Adrenal Cortex Neoplasms↗
PubMed1981

Carcinogenic effect of nitrosopyrrolidine, nitrosopiperidine and nitrosohexamethyleneimine in Fischer rats.

Three homologous cyclic nitrosamines, nitrosopyrrolidine, nitrosopiperidine and nitrosohexamethyleneimine, were administered to groups of 20 female F344 rats in drinking water, as 0.9 mM solutions. Treatment with the latter 2 compounds lasted 28 weeks, at which time several animals had died with esophageal tumors. All of the animals in these 2 groups were dead by the 36th week of the experiment. Most of the animals given nitrosohexamethyleneimine also had angiosarcomas of the liver, and a few hepatocellular carcinomas were seen. Treatment with nitrosopyrrolidine lasted 50 weeks and the first animal in the group died at the 63rd week with an hepatocellular carcinoma. By the 110th week, almost all of these animals had died with the same type of tumor, and the 2 survivors were then killed. Many of the hepatocellular carcinomas had metastasized. There were no tumors of the liver in the rats treated with nitrosopiperidine.

Animals↗
PubMed1981

Comparative carcinogenesis by some aliphatic nitrosamines in Fischer rats.

The carcinogenic effectiveness of 5 simple aliphatic nitrosamines was compared by feeding to groups of 20 Fischer rats in drinking water. Nitrosodi-isobutylamine was by far the weakest carcinogen, giving rise after comparatively high doses to tumors of the nasal cavity and trachea. Nitrosodimethylamine (NDMA) induced almost exclusively hemangiosarcomas of the liver, whereas nitrosodiethylamine (NDEA) gave rise to a high incidence of hepatocellular carcinomas, after administration of approximately the equivalent dose; all of the animals also developed tumors of the esophagus. Nitrosomethylethylamine (NMEA) induced both hemangiosarcomas and hepatocellular carcinomas, together with some esophageal tumors, but must be considered a weaker carcinogen than the dimethyl or diethyl analogs, since a much higher dose was needed to achieve a comparable effect. Nitrosodi-n-propylamine (NDPA) was of comparable potency with NDMA and NDEA, but gave rise under these conditions only to tumors of the esophagus and forestomach, and induced no liver tumors.

Animals↗
PubMed1981

Carcinogenicity of picloram.

Two studies of the carcinogenicity of the herbicide picloram in animals were reviewed. Examination of histological sections showed that picloram is highly carcinogenic in rats and mice. Neoplasms at all sites, including malignant neoplasms, were increased in male and female rats given both low and high doses of picloram in the National Cancer Institute rat study. The malignant neoplasms were both carcinomas and sarcomas. Neoplasms of the endocrine organs, particularly carcinomas, were increased in male and female rats given picloram. These carcinomas were observed in the adrenal, thyroid, and pituitary glands. Neoplasms were also increased in the liver of male and female rats and in the reproductive organs of female rats given picloram. Male and female mice exposed to picloram developed neoplasms of the spleen in the National Cancer Institute mouse study. There were also toxic changes in rats and mice. Male rats had chronic renal disease, parathyroid hyperplasia, and polyarteritis. There was atrophy of the testes in both male rats and mice given picloram.

Animals↗
PubMed1981

The effect of 4-substitution on the carcinogenicity of nitrosopiperidine.

Nitrosopiperidine and three derivatives substitute in the 4-position were fed to female F 344 rats in drinking water at equimolar concentration. The substituents were phenyl, cyclohexyl and tertiary-butyl. Like nitroso-piperidine, the t-butyl-and phenyl-derivatives induced tumors of the upper gastrointestinal tract (esophagus, forestomach and tongue), but the animals given nitroso-piperidine died earlier and after a smaller total dose. The rats given 4-phenylnitrosopiperidine also had a high incidence of tumors of the liver, both hepatocellular carcinomas and angiosarcomas. These tumors were absent from untreated animals of this strain. In contrast, no induced tumors were observed in rats treated with 4-cyclohexylnitrosopiperidine.

Animals↗
PubMed1981

Fluoro-substituted N-nitrosamines. 1. Inactivity of N-nitrosobis(2,2,2-trifluoroethyl)amine in carcinogenicity and mutagenicity tests.

N-Nitroso-bis(2,2,2-trifluoroethyl)amine (hexafluorodiethylnitrosamine, 6-F-DEN) was synthesized as a derivative of diethylnitrosamine (DEN) with blocked terminal C-atoms to avoid metabolic oxidation at this site. Chronic oral administration of 6-F-DEN in drinking water did not induce tumours in Sprague-Dawley and in Fischer 344 rats. On the other hand, equimolar doses of DEN or even much lower ones are clearly carcinogenic. Mutagenicity tests using Salmonella typhimurium strains TA 1535 and TA 100 and metabolic activation by rat liver S-9 fraction were equally negative with 6-F-DEn. The substitution of fluorine in the beta-position of DEn apparently inhibits the alpha-oxidation considered necessary for carcinogenesis and mutagenesis of dialkylnitrosamines.

Animals↗
PubMed1981

Spontaneous hyperplastic and neoplastic lesions of the uterus in mice.

A histologic study was done on the spontaneously occurring hyperplastic and neoplastic lesions of the uterus, cervix, and vagina taken from a variety of inbred, hybrid, and backcross female mice. The most commonly observed neoplasm of the endometrium was stromal cell sarcoma, followed by adenocarcinoma, which occurred approximately half as frequently. Hyperplasia was the most commonly observed endometrial lesion occurring either as glandular, stromal, or both and was often cystic with the formation of polyps. Among the benign and malignant lesions other than endometrial, leiomyomas, hemangioendotheliomas and leiomyosarcomas were the most commonly encountered. Lesions in the mucosal cervix and vagina were comparatively rare and were observed in only a few animals. Females with hyperplastic and neoplastic lesions of the uterus, cervix, and vagina in this survey represented a small fraction of the large number of animals necropsied, emphasizing the relative infrequency of these spontaneous lesions in mice.

Animals↗
PubMed1981

Carcinogenicity of dichlorvos.

Dichlorvos, 2,2-dichlorovinyl dimethyl phosphate, an organophosphate insecticide, is widely used for the control of agricultural, industrial, and domestic pests (Fig. 1) [1]. Dichlorvos is administered orally as an anthelmintic to swine, horses, cats, and dogs. It is applied by dermal application to cattle, goats, sheep, swine, and chickens to control fleas, flies, and mites. Cucumbers, radishes, lettuce, and tomatoes are treated with dichlorvos in greenhouses. Aerosols and strips are used for the control of ants, bedbugs, ticks, cockroaches, flies, mosquitoes, silverfish, spiders, and wasps. Exposure to dichlorvos is by the inhalation of sprays or vapors from impregnated resins, by skin contact, or orally as a residue in food. The predominant mode of toxicity of dichlorvos is inhibition of cholinesterase. This review includes, to the best of our knowledge, every study on the carcinogenicity of dichlorvos in animals. The studies reviewed are: NCI Dichlorvos Rat Study, Tunstall Laboratory Dichlorvos Rat Study, Kettering Laboratory Dichlorvos Rat Study, Kettering Laboratory Dichlorvos Dog Study, Shell Chemical Company Dichlorvos Swine Study, and NCI Dichlorvos Mouse Study. The conclusions from the NCI Dichlorvos Rat Study and the NCI Dichlorvos Mouse Study are based on my examination and diagnosis of the histological sections. Statistical tests of significance were obtained with Fisher's exact test, and tests for positive linear trend and departure from linear trend.

Adenoma↗
PubMed1981

Induction of carcinogenesis in Fischer rats by methylalkylnitrosamines.

Five nitrosomethyl-n-alkylamines with long aliphatic chains were administered to male F344 rats by gavage for 30 weeks. The rats treated with nitrosomethyl-n-octylamine and nitrosomethyl-n-nonylamine died within one year, while a majority of those given nitrosomethyl-n-decylamine, nitrosomethyl-n-dodecylamine, and nitrosomethyl-n-tetradecylamine lived for more than 80 weeks. Apart from the spontaneous tumors found in untreated rats of this strain, the rats treated with all four compounds containing an even number of carbon atoms in the long chain developed a high incidence of transitional cell carcinoma of the bladder. In addition, the rats treated with nitrosomethyloctylamine developed tumors of the liver (hepatocellular carcinomas and some angiosarcomas), lung, and nasal cavity. Nitrosomethylnonylamine failed to induce tumors in the bladder but induced tumors of the liver (hepatocellular carcinomas and cholangiocarcinomas), lung tumors, and some tumors of the nasal cavity.

Adenocarcinoma↗
PubMed1981

Dose response studies of carcinogenesis in rats by nitrosodiethylamine.

A dose-response study was conducted in Fischer rats with nitrosodiethylamine, which was administered in regulated amounts as a solution in drinking water. Groups of 20 female rats each received a different treatment, one group consisted of 12 animals; one of the groups was untreated. The concentrations of the solutions fed ranged from 113 to 0.45 mg/liter at six successive concentrations differing from a factor of 2.5. The treatment times were 17 weeks at the highest concentration; 22 weeks with 45 mg/liter; and 30 weeks with 18, 7, 2.8, 1.1 and 0.45 mg/liter. The two lowest dose levels were also given for 60 weeks, and the 0.45-mg/liter dose was given for 104 weeks. Animals were allowed to die naturally with tumors, and the time to death with tumors was an index of the potency of treatment. In the top four treatment groups, the potency measured in this way was proportional to the total dose of carcinogen administered. At all other doses, survival time was much less dependent on the dose administered, whether or not tumors were induced by the treatment. The principal tumors found were in the upper gastrointestinal tract, mainly the esophagus, at all doses. In the two highest dose groups, there was a high incidence of liver tumors also. There were few liver tumors in the lower dose groups, but there was a dose-related incidence of tumors of the upper gastrointestinal tract. It was remarkable that a nitrosodiethylamine concentration of 0.45 mg/liter (0.45 ppm) administered for 104 weeks induced tumors of the upper gastrointestinal tract in 70% of the treated rats.

Animals↗
PubMed1981

Carcinogenesis by derivatives of 1-nitroso-3,5-dimethylpiperazine in rats.

Four mononitrosopiperazines were administered to groups of 20 female Fischer 344 rats to compare their effectiveness as carcinogens. The four, 1-nitroso-3,5-dimethylpiperazine, its 4-acetyl derivative, its 4-benzoyl derivative, and 1-nitroso-3,4,5-trimethylpiperazine, were given as 0.7 mM solutions in drinking water, 100 ml to each rat per week. The length of treatment varied from 26 weeks for nitrosotrimethylpiperazine to 50 weeks for 1-nitroso-3,5-dimethyl-4-benzoylpiperazine. Dimethyl- and trimethylnitrosopiperazine gave rise to virtually 100% incidence of undifferentiated lymphomas of the thymus and leukemias within 30 weeks (in contrast to the non-C-methylated analogs which are noncarcinogenic or only weakly so). Acetyldimethylnitrosopiperazine was also a potent carcinogen, all of the rats treated with it dying within 30 weeks with tumors of the esophagus. In contrast, benzoyldimethylnitrosopiperazine was weakly carcinogenic, inducing only a small number of tumors of the forestomach and reducing the normal life span of the rats very little.

Animals↗
PubMed1980

Potent carcinogenicity of nitrosodiethanolamine in rats.

Nitrosodiethanolamine is found in synthetic cutting oils and in many cosmetic preparations and is probably the N-nitroso compound to which human exposure is greatest. It is formed by reaction of the commonly used amines diethanolamine and triethanolamine with nitrosating agents. An assessment of the possible risk in human exposure to nitrosodiethanolamine must be based on sound chronic toxicity data. A previously published chronic test of this compound in rats has shown it to induce liver tumours after very high oral doses, and tumours of the nasal cavity after administration of high repeated doses to Syrian hamsters by subcutaneous injection. To improve our understanding of the carcinogenic potency of nitrosodiethanolamine, we undertook a more extensive study, in which the compound was administered at concentrations ranging from 3,900 to 31,250 parts per million (p.p.m.) in drinking water, to groups of rats for about 6 months. We report here that when the animals were killed, all bore hepatocellular carcinomas, many of which metastasized at the higher doses, indicating that nitrosodiethanolamine is a carcinogen of considerable potency in the rat. However, it is inactive or very weakly active in short-term tests, such as the Salmonella mutagenesis test developed by Ames.

Animals↗
PubMed1980

Liver tumors induced in rats by oral administration of the antihistaminic methapyrilene hydrochloride.

The antihistaminic over-the-counter drug methapyrilene hydrochloride, mixed with food at a concentration of 0.1 percent, was administered to 50 male and 50 female Fischer rats. A second group of 50 male and 50 female rats was given the same treatment together with 0.2 percent of sodium nitrite added to the food. Almost all of the rats in both groups developed liver neoplasms, mainly hepatocellular carcinomas and cholangiocarcinomas. The first rat died with a liver neoplasm at the 43rd week. Over 50 percent of the rats in both groups had metastases from the carcinomas of the liver to distant organs. Control rats treated with nitrite only, or untreated, did not develop liver neoplasms. There was no discernible effect of nitrite on the carcinogenicity of methapyrilene hydrochloride.

Aminopyridines↗
PubMed1980

Histopathology of carcinomas of the liver in mice fed perthane.

B6C3F1 female mice fed an average dose of 3,000 ppm of perthane for 2 years developed a highly significant incidence of hepatocellular carcinomas of the liver. Male mice fed 2,500 ppm perthane had a slight increase of carcinoma of the liver. Some of the carcinomas were well-differentiated; however, most were poorly differentiated or undifferentiated. Perthane-treated mice also had well and poorly differentiated cholangiocarcinomas and carcinosarcomas, neoplasms not seen in control mice.

Adenoma, Bile Duct↗
PubMed1980

The effect of deuterium labeling on the carcinogenicity of nitroso-2,6-dimethylmorpholine in rats.

Nitroso-2,6-dimethylmorpholine (Me2NMOR) was labeled with deuterium in either the alpha or beta positions. Both the deuterium-labeled, and the unlabeled, compounds were administered to female Fischer 344 rats at equimolar concentrations in drinking water. The animals were then allowed to die naturally with tumors. The parent compound and the alpha-d4-labeled derivative were given at 50 mg/liter and 20 mg/liter, while, because of a shortage of the compound, the beta-d2-labeled derivative was given only at 20 mg/liter. Almost all of the animals died with basal cell carcinomas and papillomas of the esophagus; many animals fed the lower doses also had tumors of the nasal cavity and tongue. The rate of death from induced tumors was lower in the alpha-d4-treated group than in those treated with the unlabeled compound (at both dose levels), but was higher in the rats treated with the beta-d2 compound. It appears that deuterium in the alpha positions decreases carcinogenic potency, while deuterium in the beta positions increases it. This suggests that oxidation at the beta carbon atoms is less likely to be involved in esophageal carcinogenesis in the rat by Me2NMOR than is oxidation at the alpha carbon atoms.

Animals↗
PubMed1980

Comparison of carcinogenesis by two isomers of nitroso-2,6-dimethylmorpholine.

The cis and trans isomers of nitroso-2,6-dimethylmorpholine (Me2NMOR) have been separated and administered to Fischer 344 rats at doses corresponding to their proportion in the mixture prepared from the commercial amine (approximately 2 cis to 1 trans). The mixture of isomers was given at 2 doses, 50 mg per liter of drinking water and 20 mg per liter. A standard volume of each solution was given (20 ml per day per rat) on 5 days of each week and the animals were treated for the same time at either higher or lower dose levels. Almost all of the animals died with basal cell carcinomas and/or papillomas of the upper gastrointestinal tract. The time at which the rats died with the tumors was used as a measure of carcinogenic potency. Survival of the treated animals was consistently longer at the lower dose of each isomer. It was concluded that the trans isomer of Me2NMOR is a more potent carcinogen in rats than the cis isomer.

Animals↗