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Biomedical subjects

R M Kovatch

Publications and source records attributed to R M Kovatch.

At least 73 records · Page 4Linked to original sources
PubMed1986

Carcinogenic effects of sequential administration of two nitrosamines in Fischer 344 rats.

The carcinogenic effects of sequential treatment of female F344 rats with two nitrosamines were studied. The animals received either methylethylnitrosamine (NMEA), a strong liver carcinogen, N-nitrosomethylaniline (NMA), a moderately strong esophageal carcinogen, or N-nitrosopyrrolidine, (NPyr), a weaker liver carcinogen. The sequentially treated groups were given NMEA followed by NMA and vice versa, NPyr followed by NMEA and vice versa. The dose and duration for each chemical in the sequentially treated groups were identical for the individual treatments. The animals were allowed to die or were killed when moribund. The animals surviving longer than 110 weeks were sacrificed. The NMEA-NPyr and NPyr-NMEA groups had a tumor spectrum characteristic for NMEA alone (a mixture of hepatic carcinomas and sarcomas with extensive metastases to the lungs). The survival was reduced in the NMEA-NPyr group compared to the NMEA alone group. The time to death of the NMA-NMEA group was not affected by the NMA treatment, but many of the animals had esophageal neoplasms. The NMEA-NMA group survival was reduced when compared to the NMEA alone group but the tumor spectrum was dominated by NMEA. The data indicate that when the target organ is the same, the effect of two nitrosamines is additive with the stronger carcinogen dominating the tumor spectrum. When the target organs are different, the initial exposure influences the tumor spectrum, although the treatment with the second nitrosamine enhances the tumorigenicity of the initial nitrosamine.

Animals↗
PubMed1985

Carcinogenesis by oxygenated nitrosomethylpropylamines in Syrian hamsters.

Three oxygenated propylnitrosomethylamines were administered to female Syrian hamsters at doses similar to those which had induced high incidences of esophageal neoplasms in rats. Nitrosomethyl-2-oxopropylamine (NMOP) given at the rate of 2 mg/animal/week, whether as one application of 2 mg or two applications of 1 mg, led to early death of the animals, mostly with liver neoplasms; administration of 1 mg/animal/week led to longer survival, but most animals died with both liver neoplasms and neoplasms of the nasal mucosa. Only one hamster treated with NMOP had a neoplasm of the pancreatic duct. Of the 14 hamsters treated with the higher dose of nitrosomethyl-2-hydroxypropylamine (NMHP) and surviving beyond 6 weeks, most had liver neoplasms and nine had neoplasms of the pancreatic ducts. At the lower dose of NMHP, most hamsters developed neoplasms of the nasal mucosa, as did those receiving the same dose of NMOP, and seven animals had hemangioendothelial tumors of the liver, but only one animal had a carcinoma of the pancreatic duct. Nitrosomethyldihydroxypropylamine (NMDHP) was a much weaker carcinogen than the other two compounds and induced mainly neoplasms of the nasal mucosa, with little shortening of life.

Animals↗
PubMed1985

Induction of liver tumors in rats by nitrosodiethanolamine at low doses.

Nitrosodiethanolamine was given to male and female F344 rats in drinking water at three concentrations, 160, 64 and 28 mg/l. The highest dose was given for 50 weeks, the middle dose for 50 weeks and for 100 weeks, and the lowest dose for 100 weeks, the last to a group of 39 rats of each sex. The principal neoplasms that could be attributed to the treatment were hepatocellular carcinomas and neoplastic nodules in the liver. All of the female rats and 70% of male rats drinking 160 mg/l had hepatocellular neoplasms. At 64 mg/l the incidence of hepatocellular neoplasms was higher after 100 weeks administration than after 50 weeks, and was significantly higher than in controls after 100 weeks in both sexes. At 28 mg/ml there was a greater incidence of hepatocellular neoplasms than among controls only in the female rats. Nitrosodiethanolamine appears to be carcinogenic to F344 rats at quite low concentrations.

Animals↗
PubMed1985

Similar carcinogenic effects in rats of 1-ethyl-1-nitroso-3-hydroxyethylurea and 1-hydroxyethyl-1-nitroso-3-ethylurea.

The two isomeric N-nitroso derivatives of the dialkylurea, 1-ethyl-3-(2-hydroxyethyl)urea, were given by gavage to 20 male F344 rats for 30 weeks at equimolar doses. The tumorigenic responses were compared with those to a similar dose of nitrosoethylurea or nitroso-2-hydroxyethylurea. Each of the nitrosomonoalkylureas caused death from tumors more rapidly than the analogous nitrosodialkylurea. Each of the nitrosodialkylureas induced a broader spectrum of tumors in the rats than did either nitrosoethylurea or nitroso-2-hydroxyethylurea, including neoplasms of the thyroid, lung, skin, colon, mesotheliomas and neoplasms of the brain and liver in high incidence, the last two of which were not seen in animals given the nitrosomonoalkylureas. On the other hand, there were fewer tumors of the forestomach in rats given the nitrosodialkylureas than with the nitrosomonoalkylureas. The major difference between 1-nitroso-1-ethyl-3-hydroxyethylurea and 1-nitroso-1-hydroxyethyl-3-ethylurea was that the former induced only neoplastic nodules in the liver of 30% of the rats, while the latter induced hepatocellular carcinomas in 55% of the rats; approximately half of the rats given either compound had brain neoplasms, which included astrocytomas, gliomas and oligodendrogliomas.

Animals↗
PubMed1985

Comparative carcinogenesis by hydroxylated nitrosopropylamines in Syrian hamsters.

The relationship between the chemical structure of nitrosamines and their carcinogenic activity has been examined in Syrian golden hamsters in parallel with similar studies in rats to aid in explaining the sharp interspecies differences in response to these compounds. The relationship between the beta-oxidized N-propyl-nitrosamine structure and the induction of tumors of the pancreatic duct in Syrian golden hamsters was investigated by administration of a number of asymmetric acyclic nitrosamines containing that structure to female hamsters for 29-50 weeks. N-Nitroso-2-oxopropyl-2-hydroxyethylamine (OPE), N-nitroso-2-hydroxypropyl-2-hydroxyethylamine (NIEA), and N-nitroso-2,3-dihydroxypropyl-2-oxopropylamine (DHPOP) induced pancreatic tumors. OPE also induced a high incidence of liver neoplasms, and a number of animals given NIEA and N-nitrosoallyl-2-oxopropylamine (NAOP) also had liver neoplasms. N-Nitroso-2,3-dihydroxypropyl-2-hydroxyethylamine was very weakly carcinogenic. N-Nitroso-2,3-dihydroxypropyl-2-hydroxypropylamine and DHPOP induced a high incidence of neoplasms of the forestomach (mainly papillomas). N-Nitrosoallyl-2,3-dihydroxypropylamine, N-nitrosoallyl-2-hydroxypropylamine, and NAOP induced primarily neoplasms of the nasal mucosa but no neoplasms of the pancreatic ducts in hamsters.

Animals↗
PubMed1985

Immunocytochemical localization of the surfactant apoprotein and Clara cell antigen in chemically induced and naturally occurring pulmonary neoplasms of mice.

The localization of surfactant apoprotein (SAP) and the Clara cell antigen(s) (CCA) was studied in naturally occurring and experimentally induced pulmonary hyperplasias and neoplasms by avidin-biotin peroxidase complex (ABC) immunocytochemistry. Lungs of B6C3F1 and A strain mice with naturally occurring lesions, B6C3F1 mice given injections of N-nitrosodiethylamine (DEN), BALB/c nu/nu or nu/+ mice exposed transplacentally on Day 16 of gestation to ethylnitrosourea (ENU), or BALB/c nu/+ mice exposed to ENU at 8-12 weeks of age were preserved in formalin or Bouin's fixative. After ABC immunocytochemistry, SAP was found in the cytoplasm of normal alveolar Type II cells; in the majority of cells in focal alveolar and solid hyperplasias originating in peribronchiolar or peripheral locations; and in solid, tubular, papillary, and mixed adenomas and carcinomas. The larger mixed-pattern neoplasms and small or large tubular neoplasms usually had the least number of cells with SAP. The majority of large papillary adenomas and carcinomas in BALB/c mice exposed to ENU and in untreated A strain mice contained SAP in the nuclei of many neoplastic cells but only in the cytoplasm of a few neoplastic cells. CCA was found in normal Clara cells of bronchi and bronchioles but not in any hyperplastic or neoplastic lesion of any mouse studied. This study provided immunocytochemical evidence that the vast majority of naturally occurring and experimentally induced pulmonary neoplasms of mice are alveolar Type II cell adenomas and carcinomas.

Adenoma↗
PubMed1985

Carcinogenic effect of nitrosoalkylureas and nitrosoalkylcarbamates in Syrian hamsters.

Three nitrosoalkylureas, two nitrosotrialkylureas, and three nitrosoalkylcarbamates were given to Syrian golden hamsters by gavage at approximately equimolar doses. Measured by the time to death with tumors as an index, nitrosoethylurea was the most potent carcinogen, followed by nitroso-2-hydroxyethylurea, which was less effective in males than in females. The least effective compounds, by this measure, were nitrosooxazolidone and nitroso-5-methyloxazolidone. The remaining compounds, nitroso-N-ethylurethan, nitroso-2-hydroxypropylurea, nitrosomethyldiethylurea, and nitrosotriethylurea appeared to be of similar potency. All of the compounds induced papillomas or carcinomas of the nonglandular stomach in high incidence, except in the groups given nitrosohydroxyethylurea or nitrosooxazolidone; exceptionally, only 35% of the latter group had tumors, compared with 70% or more in the other groups. All of the nitrosoalkylureas induced a high incidence of hemangiosarcomas of the spleen, but the nitrosoalkylcarbamates did not. The quite uniform response of the hamster to these compounds contrasts with the great variety of organs and cell types in which they induce tumors in the rat.

Animals↗
PubMed1984

Carcinogenesis by nitrosomorpholines, nitrosooxazolidines and nitrosoazetidine given by gavage to Syrian golden hamsters.

Five cyclic nitrosamines, four containing oxygen in the ring, were administered by gavage to groups of 20 male Syrian golden hamsters. After administration of very similar doses, nitrosomorpholine, nitroso-2-methylmorpholine and nitroso-5-methyl-1,3-oxazolidine caused the animals to die with tumors after similar times, but nitrosomorpholine induced mainly tumors of the nasal cavity (and a few of the trachea), whereas the 2-methyl derivative induced tumors of the nasal cavity and liver. While nitroso-1,3-oxazolidine and its 5-methyl derivative both induced liver tumors (but no tumors in the nasal cavity) those induced by the former compound took much longer to kill the animals. Nitrosoazetidine, a liver carcinogen in rats, but which had been reported to be inactive in hamsters, did induce tumors of the liver in 30% of hamsters after a much larger dose than the other cyclic nitrosamines.

Animals↗
PubMed1984

Comparison of the carcinogenic effectiveness of N-nitrosobis(2-hydroxypropyl)amine, N-nitrosobis(2-oxopropyl)amine, N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine, and N-nitroso-2,6-dimethylmorpholine in Syrian hamsters.

For examination of metabolic interrelationships in carcinogenesis between N-nitroso-2,6-dimethylmorpholine, N-nitrosobis(2-oxopropyl)amine (CAS: 60599-38-4), N-nitrosobis(2-hydroxypropyl)amine (CAS: 53609-64-6), and N-nitroso(2-hydroxypropyl) (2-oxopropyl)amine, each was given to a separate group of 20 female Syrian golden hamsters by gavage. All four compounds induced tumors of the pancreatic duct and lung tumors, but the incidences varied from one compound to another. In addition, N-nitrosobis(2-oxopropyl)amine and N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine induced many hepatocellular and cholangiocellular neoplasms, which the other two compounds did not. On the basis of short time to death with tumors and the relatively low total dose administered, N-nitrosobis(2-oxopropyl) amine appeared to be the most potent carcinogen in the hamster among the four. N-nitroso(2-hydroxypropyl)(2-oxopropyl)amine was next in potency but was considerably weaker than N-nitrosobis(2-oxopropyl)amine. N-Nitroso-2,6-dimethylmorpholine, which was similar in potency to N-nitroso(2-hydroxypropyl) (2-oxopropyl)amine, however, did not induce a significant incidence of liver tumors of any type; and N-nitrosobis(2-hydroxypropyl) amine was considerably less potent than the other three compounds. These results did not support the opinion of N-nitroso(2-hydroxypropyl) (2-oxopropyl)amine as the proximate carcinogenic metabolite of all three compounds in the Syrian hamster but instead suggested that these compounds might have acted through formation of different and yet unknown carcinogenic intermediates.

Animals↗
PubMed1983

Haemorrhagic syndrome in cattle associated with Trypanosoma vivax infection.

Trypanosoma vivax isolated from dairy cattle undergoing a haemorrhagic disease was inoculated into Ayrshire steers. Five of six infected animals experienced brief periods of diarrhoea and sublingual and gastro-intestinal haemorrhage. Gastro-intestinal bleeding coincided with markedly reduced numbers of thrombocytes and a high level of parasitaemia in the peripheral blood. Prothrombin times were extended and fibrinogen levels were elevated in infected animals. Plasma paracoagulation tests were positive for the presence of fibrin monomers and/or clottable early fibrin degradation products during the course of infection.

Animals↗
PubMed1981

Acute Trypanosoma vivax infection in dairy cattle in Coast Province, Kenya.

In an outbreak of a fatal haemorrhagic disease in exotic dairy cattle (Friesian, Guernsey, Ayrshire and Jersey) on 2 farms in the Coast Province of Kenya, and investigation was conducted to establish the aetiological agent involved. Blood and lymph node smears made from clinically sick cattle indicated infection with Trypanosoma vivax. Five calves were then experimentally inoculated with heparinised blood from cows naturally infected with T. vivax. All calves had a high T. vivax parasitemia, marked depression and fever; 2 developed blood-tinged diarrhoea 6 and 7 days were treated with isometamidium chloride while others were left untreated. Cases of abortions, bloody diarrhoea and deaths dropped markedly in the treated animals whereas they continued to occur in the untreated animal.

Acute Disease↗
PubMed1977

Myopathy in guinea pigs.

Myopathy resembling nutritional muscular dystrophy occurred in a colony of 150 guinea pigs. Of 54 animals affected, 27 died. Major clinical signs were depression, conjunctivitis, and reluctance to move. Lesions were widespread throughout skeletal and cardiac musculature. Clinical signs and deaths ceased when the diet was changed to a different commercial ration. A single intramuscular injection of sodium selenite and alphatocopherol brought prompt remission of clinical signs in one group of 20 so treated.

Animal Feed↗
PubMed1976

Spontaneous tumors in the Dunkin-Hartley guinea pig.

Seventy-nine spontaneous neoplasms in Dunkin-Hartley guinea pigs were observed over a 9-year period in the Fort Detrick guinea pig colony. Sixty-three of the neoplasms were found during approximately 8,500 necropsies performed on animals under 27 months of age. The remaining 16 tumors were in 34 breeders maintained after 27 months of age on a natural life-span study. Of this group, 10 (29.4%) developed neoplasms by the termination of the study, when the animals were 80 months of age. The skin tumor, trichofolliculoma, of which there were 29, comprised the largest tumor classification.

Age Factors↗