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Biomedical subjects

M D Reuber

Publications and source records attributed to M D Reuber.

At least 73 records · Page 4Linked to original sources
PubMed1980

Carcinogenicity of the isomeric, N-nitroso-delta3-and N-nitroso-delta2-piperidines in rats and the in vivo isomerization of the delta3-to the delta2-isomer.

N-Nitroso-1,2,3,6-tetrahydropyridine (N-nitroso-delta3-piperidine), N-nitroso-1,2,3,4-tetrahydropyridine (N-nitroso-delta2-piperidine) and N-nitroso-3,4-epoxypiperidine were tested for carcinogenicity in Fischer 344 rats. The unsaturated nitrosamines were administered in drinking water (100 mg/l). The epoxide was administered by gavage in corn oil (11.5 mg/ml, 0.2 ml twice a week). Both of the unsaturated nitrosamines were potent carcinogens (most of the animals died by the 35th week), and both produced many esophageal tumors, a property which they have in common with the parent compound, N-nitrosopiperidine. The spectrum of the other tumors formed, however, was different. The delta3-isomer produced hemangioendothelial sarcomas in the liver, which were absent in the tumor spectrum of the delta2-isomer and N-nitrosopiperidine. The delta2-isomer, on the other hand, produced tumors of the forestomach and the oropharynx, which were essentially absent in the rats treated with the delta3-isomer. N-nitroso-3,4-epoxypiperidine was a toxic compound (8 deaths in the first 5 weeks), but most of the remaining animals survived to 40 weeks. Of these, 8 animals died of induced tumors (esophagus and liver). The delta2- and the delta3-isomers were administered by gavage to groups of rats and the blood of these animals was withdrawn at timed intervals. Analysis of the serum revealed that both of the nitrosamines were cleared rapidly from circulation but that at the same time the delta3-isomer was being isomerized to the delta2. The reverse transformation did not occur in vivo.

Animals↗
PubMed1980

Carcinogenicity of deuterium-labeled N-nitroso-N-methylcyclohexylamine in rats.

F344 rats were treated with both unlabeled N-nitroso-N-methylcyclohexylamine (NMC) and deuterium-labeled NMC (NMC-d3) in the methyl group. Both compounds were administered in the drinking water at concentrations of 50 and 12.5 mg/liter. The NMC-d3 was not less carcinogenic than the unlabeled NMC, which suggested that oxidation of the methyl group is not a rate-limiting step in the induction of esophageal tumors.

Animals↗
PubMed1980

Adenocarcinoma of the kidney. III. Histogenesis of renal adenocarcinomas induced in rats by N-(4'-fluoro-4-biphenylyl)acetamide.

The histogenesis of renal adenocarcinoma induced in F344 rats by the carcinogen N-(4'-fluoro-4-biphenylyl)acetamide (FBPA) was described in order to clarify the site of origin of this neoplasm within the nephron. FBPA was added to the diet up to 48 weeks, and the animals were killed at intervals from 4 to 52 weeks after initiation of the carcinogenic diet. As seen by light microscopy, tumors appeared to arise from the pars recta of the proximal tubule in a series of stages progressing from focal hyperplasia with dysplasia to development of small, then large, neoplastic nodules composed of moderately basophilic, closely packed tumor cells arranged in individual aggregates or lobules surrounded by basement membrane-like material. Karyomegaly, cystic lesions, foam cell lesions, interstitial fibrosis, and casts also accompanied tumorigenesis in this animal model.

Adenocarcinoma↗
PubMed1980

Carcinogenicity and toxicity of methoxychlor.

Methoxychlor is carcinogenic for the liver of C3H and BALB/c mice and Osborne-Mendel rats, and possibly for the liver of dogs. Methoxychlor is also carcinogenic for the testis of BALB/c male mice, bone of B6C3F1 female mice, and the ovary of Osborne-Mendel female rats. The incidences of carcinomas of the liver were increased in C3H male mice and BALB/c male and female mice fed methoxychlor. There also was an increase in malignant neoplasms at all sites in BALB/c male and female mice. C3H and BALB/c male mice were more susceptible to the carcinogenic effects of methoxychlor than were female mice. BALB/c mice were more susceptible than C3H mice. Osborne-Mendel male and female rats developed significant incidences of carcinomas of the liver. The incidence of sarcomas of the spleen and abdomen, mostly hemangiosarcomas, was increased in male rats. Neoplasms of the pituitary, adrenals, and mammary gland were also increased in methoxychlor-treated female rats. Miniature swine given methoxychlor developed chronic renal disease in relatively short periods of time. There also was hyperplasia of the mammary gland and uterus, suggesting an estrogen-like effect on those organs. Methoxychlor applied to the skin of rabbits caused a dose-related atrophy of the testes, as well as chronic renal disease. Atrophy of the testes and chronic renal disease could not be evaluated in mice and rats because of insufficient data.

Animals↗
PubMed1980

Significance of acute and chronic renal disease in Osborne-Mendel rats ingesting dieldrin or aldrin.

Renal lesions developed in Osborne-Mendel male and female rats ingesting dieldrin or aldrin in the diet. Chronic interstitial nephritis was seen in rats surviving for 52 wk or longer. The incidence of nephritis was highest and the lesion was most severe in male rats given the higher dose levels of dieldrin, 50 ppm or higher. Over one-half of the rats fed dieldrin or aldrin at 150 ppm, and many fed 100 ppm, died from renal necrosis and sometimes hepatic necrosis during the first year. More female rats died from renal necrosis than did male rats. Rats dying from renal necrosis did not develop tumors; those from severe chronic nephritis either did not have tumors or had preneoplastic lesions that would have become tumors if the animal had lived longer. Thus acute and chronic effects should both be examined carefully when evaluating the safety of a chemical. In addition to causing the death of the animal, acute and chronic toxic effects can prevent the development of malignant tumors by shortening the animal's life span or by causing illness and inhibiting the development of a tumor that otherwise might occur in a healthy animal.

Aldrin↗
PubMed1980

Carcinogenicity of benzene hexachloride and its isomers.

Technical BHC and the alpha, beta, gamma and delta isomers of BHC are carcinogenic for the liver of mice and rats. Mice given the isomers of BHC developed carcinomas and hyperplastic nodules of the liver as early as 24 weeks. Several strains of mice (dd, ICR-JLC, CL1, DDY, IRC, DBA/Z, C3H/HEN, C57BL/6 were susceptible. Male mice were more susceptible to hepatic carcinogenesis than female mice and they appeared to be more susceptible to alpha-BHC. The incidence of neoplasms of the liver was increased when beta-, gamma-, or delta-BHC were each given together with alpha-BHC. PCB-5 promoted the induction of hepatic neoplasms when administered with beta-BHC. Technical BHC and its isomers are carcinogenic for the liver of male and female Wistar rats. Beta-BHC is carcinogenic for the liver of Osborne-Mendel male rats. Osborne-Mendel rats receiving delta-BHC developed cirrhosis of the liver, portal vein thrombosis, and focal necrosis of the skeletal muscle. Male rats ingesting technical BHC or the beta or delta isomers also had atrophic testes.

Animals↗
PubMed1980

Carcinogenicity of nitrosotrialkylureas in Fischer 344 rats.

Three nitrosotrialkylureas were administered to female F344 rats as approximately 1-mM solutions in drinking water. Nitrosotrimethylurea, given for 47 weeks, gave rise to astrocytomas of the brain and tumors of the forestomach; nitrosotriethylurea induced a high incidence of adenocarcinomas of the breast and uterus and tumors of the forestomach. Nitrosomethyldiethylurea induced almost exclusively a high incidence of both astrocytomas of the brain and tumors of the spinal cord.

Animals↗
PubMed1980

Carcinogenicity in rats of nitrosomethylethylamines labeled with deuterium in several positions.

Nitrosomethylethylamine and four of its derivatives labeled with deuterium at various positions were administered to male Fischer 344 rats in drinking water at equimolar doses for 30 weeks. The doses were 30 and 6 mg/liter at the rate of 3 and 0.6 mg/week, approximately. The rats receiving the higher doses died earlier and had more tumors than those given the lower doses. At both dose levels, nitrosomethylethyl-1-d2-amine and nitrosomethylethyl-d5-amine were more effective carcinogens than was unsubstituted nitrosomethylethylamine. Rats died earlier and more of them had tumors after receiving the deuterium-labeled compounds. Nitrosomethyl-d3-ethylamine and nitrosomethyl-d3-ethyl-d5-amine did not greatly differ in carcinogenic effectiveness from the unsubstituted compound. Both nitrosamines having deuterium in the methyl portion of the ethyl group, nitrosomethylethul-d5-amine and nitrosomethyl-d3-ethyl-d5-amine, induced esophageal tumors as well as liver tumors in the rats.

Animals↗
PubMed1980

Carcinogenicity of 3-chloronitrosopiperidine, 4-chloronitrosopiperidine, and 3,4-dichloronitrosopiperidine in Fischer rats.

Three chlorinated nitrosopiperidines, 3-chloro-, 4-chloro-, and 3,4-dichloronitrosopiperidine, were administered to groups of 20 male Fischer 344 rats at a concentration of 0.17 mM in drinking water. Treatment with the monochloro compounds lasted for 30 weeks, while treatment with the dichloro compound lasted for 21 weeks. Almost all of the animals died with esophageal tumors. There was also a significant incidence of tumors of the forestomach and tongue in the rats treated with the monochloro compounds. Using the rate of death of the animals with tumors as an index, the relative potency of the three compounds increases from 3-chloro- to 4-chloro- to 3,4-dichloronitrosopiperidine.

Animals↗
PubMed1979

Interstitial cell carcinomas of the testis in Balb/C male mice ingesting methoxychlor.

Balb/c and C3H strains male and female mice ingested 750 ppm methoxychlor or 100 ppm DDT in the diet for 2 years. Balb/c strain male mice ingesting methoxychlor developed a highly significant incidence of interstitial cell carcinomas of the testis. Balb/c strain male mice ingesting DDT and C3H strain male mice receiving methoxychlor or DDT did not have testicular tumors. The carcinomas of the testis varied from well-differentiated to poorly differentiated and undifferentiated and were capable of metastasis. Carcinomas of the testis have been described in Balb/c strain male mice, but not C3H, given estrogens. The carcinogenicity for testis of Balb/c strain male mice is most likely related to the estrogenic activity of methoxychlor.

Animals↗
PubMed1979

Carcinogenicity of endrin.

Endrin is carcinogenic for rats, and most likely also for mice and dogs. Endrin caused significant incidences of malignant neoplasms at all sites. In one study, female rats were susceptible to the development of neoplasms of the endocrine organs, particularly carcinomas of the adrenal and pituitary glands as well as neoplasms of the reproductive system. In other studies, female rats tended to have carcinomas of the endocrine system, the mammary gland and reproductive system, and male and female rats lymphomas. Rats developed unusual malignant neoplasms, such as Kupffer cell sarcomas of the liver and sarcomas of the mammary gland, uterus, and stomach. There also were toxic changes, particularly in male rats, ingesting endrin. These lesions included interstitial fibrosis of the kidney; polyarteritis of the mesenteric, pancreatic and other arteries; and atrophy of the testes. Such lesions generally interfere with the health of the rats and with the development of neoplasms. Dog receiving endrin for two years had bone marrow hyperplasia, lesions of the thyroid gland and lesions of the skeletal muscle, and hyperplasias or neoplasms of other organs. One female dog had an early carcinoma of the thyroid gland. Mice ingesting endrin developed increased incidences of carcinomas of the liver and sarcomas of the uterus.

Adenoma↗
PubMed1979

Carcinogenicity of toxaphene: a review.

Toxaphene is highly carcinogenic in rats and mice. Toxaphene induced malignant neoplasms of the liver in rats. Neoplasms at all sites, as well as malignant neoplasms, were increased in male and female rats ingesting toxaphene. Sarcomas were found more often in male rats and carcinomas in female rats. Neoplasms of the endocrine organs were also increased in male and female toxaphene-treated rats. The incidence of neoplasms of the reproductive system was increased in female rats, as was the incidence of mammary gland neoplasms in male rats. Toxic changes in male rats given toxaphene included interstitial fibrosis of the kidney and atrophy of the testes. Toxaphene induced malignant neoplasms of the liver in male and female mice. The incidence of malignant neoplasms at all sites was also increased. In addition to hepatic neoplasms, male mice had leukemia or lymphosarcoma and females had sarcomas of the uterus.

Adrenal Gland Neoplasms↗
PubMed1979

Neoplasms of the forestomach in mice ingesting dihydrosafrole.

The maximal tolerated doses of dihydrosafrole, safrole, and isosafrole were given by continuous oral administration, starting at the age of 7 days, to both sexes of two hybrid strains of mice - (C57BL/6 X C3HAnf)F1 and (C57BL/6 X AKR)F1. Hyperplasia and carcinomas of the forestomach were significantly increased in female mice of both strains and in male mice of the latter strain ingesting dihydrosafrole. By contrast, neoplasms of the forestomach were not increased in mice receiving safrole or isosafrole. Mice with neoplasms of the stomach generally did not have neoplasms of the liver.

Animals↗
PubMed1979

Carcinogenicity of chloroform.

Chloroform is carcinogenic in rats, mice, and probably in dogs. Chloroform induced carcinomas of the liver and kidney and malignant tumors in other organs in rats and mice. Liver neoplasms have been described in three strains of mice. Carcinomas of the kidney were found in a first study in mice and in the repeat of that study. Dogs given chloroform developed neoplasms of the liver as well as in other organs. Rats given chloroform also developed toxic changes, particularly male rats, as a result of treatment. These lesions included interstitial fibrosis of the kidney; polyarteritis of the mesenteric, pancreatic, and other arterioles and arteries; and atrophy of the testes. These toxic changes may have interfered with the development of neoplasms in male rats.

Adenoma, Bile Duct↗
PubMed1979

Histopathology of liver carcinomas in (C57BL/6N X C3H/HeN)F1 mice ingesting chlordane.

(C57BL/6N X C3H/HeN)F1 male mice that ingested 30 or 56 ppm chlordane and female mice that ingested 30 or 64 ppm chlordane in the diet had highly significant incidences of carcinomas of the liver. The carcinomas varied from well differentiated to poorly differentiated and undifferentiated and were capable of invasion and metastasis. They were more poorly differentiated in mice receiving chlordane than in controls.

Animals↗