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Biomedical subjects

T Ogiu

Publications and source records attributed to T Ogiu.

At least 55 records · Page 3Linked to original sources

Relation between development of leukemia and duration of N-nitroso-N-ethylurea treatment in DONRYU rats.

N-Nitroso-N-ethylurea (NEU; CAS: 759-73-9) is a strong leukemogen that induces erythroblastic leukemia in inbred DONRYU rats. In the present experiments, relationships between development of leukemia, duration of NEU treatment, and sequential changes in the hematopoietic organs during carcinogen administration were examined. In experiment 1, groups of rats were given a 400-ppm NEU solution for 0, 2, 4, 6, 8, or 10 weeks, and the resultant incidence of leukemias was 0, 26, 40, 75, 95, and 100%, respectively. Of the various types of leukemia, the erythroblastic type was observed in 0, 0, 20, 40, 95, and 90% of rats, respectively. The average latent period showed an inverse correlation with the duration of NEU treatment. In experiment 2 the animals were divided into carcinogen-treated and control groups, and rats were sacrificed periodically for histopathologic examination. In the experimental group, the bone marrow became hypoplastic soon after commencement of NEU treatment and at the 6th week became severely aplastic, thereafter recovering slightly. At the 10th week, 2 rats out of 5 examined were leukemic. Relationships between incidence of leukemia, duration of NEU treatment, and sequential changes of the bone marrow during carcinogen administration are discussed.

Animals↗

Malignant fibrous histiocytomas induced in rats by polymers.

Five polymeric materials (3 polyvinyl chlorides, 1 polyhydroxyethyl methacrylate, and 1 dimethyl polysiloxane) were implanted into subcutaneous (SC) tissues of rats. Subcutaneous tumors developed in all experimental groups. The incidences of the tumors differed however, although the experimental conditions were the same for all these materials. This result indicates that chemical characteristics of the materials may influence the incidence of SC tumors. From the histological and electron-microscopic findings many of these tumors were diagnosed as malignant fibrous histiocytomas.

Animals↗

Induction of digestive-tract tumors in F344 rats by continuous oral administration of N-butyl-N-nitrosourea.

Male and female F344/DuCrj rats were administered N-butyl-N-nitrosourea at a concentration of 400 ppm in their drinking water. By the 50th week of the experiment, the cumulative incidence of upper-digestive-tract tumors was as high as 35/39 (90%) and 34/39 (87%) in male and female rats, respectively. Among these, esophageal and forestomach tumors occurred most frequently. Except one female rat with fibroma, upper-digestive-tract neoplasms were of the epithelial type -- papilloma, squamous-cell carcinoma or adenocarcinoma. In female rats, vaginal tumors were induced in 16 (41%) animals. Ear-duct tumors and hematopoietic neoplasms were also induced in both sexes of rats, with incidence of less than 21%.

Adenocarcinoma↗

Null effects of vitamin A analogs on the dimethylnitrosamine kidney tumor model.

The effect of retinoids on the induction of both epithelial and mesenchymal tumors of the rat kidney by a single dose of 40 mg/kg dimethylnitrosamine was tested using 13-cis-retinoic acid and the trimethylmethoxy phenyl analog of retinoic acid ethylamide. 13-cis-retinoic acid was administered for 3 weeks, 10 weeks, or 26 weeks, post-carcinogen treatment, in order to coincide with known morphological phases occurring within the kidney which culminated in the development of macroscopic tumors. The ethylamide analog and placebo beadlets were administered for the 26 week period only. None of the retinoid schedules significantly influenced the survival of the animals, nor the incidences of renal mesenchymal tumors or renal cell adenomas/adenocarcinomas. Tumor latency, histological grade or frequency of metastatic invasion were also unaltered by the treatments. Possible reasons for the observed lack of effect are discussed, including speculation regarding the potency of this single-dose model of chemical carcinogenesis.

Animals↗

Foreign-body tumorigenesis in rats by various kinds of plastics--induction of malignant fibrous histiocytomas.

Five kinds of plastics (3 polyvinyl chlorides, 1 polyhydroxyethyl metacrylate and 1 dimethyl polysiloxane) were implanted into subcutaneous tissues of Wistar rats of both sexes. Subcutaneous tumors developed in all experimental groups. The incidences of the tumors, however, differed from each other, although these materials were tested on the same experimental condition. This result indicates that chemical characters of the materials may influence the incidence of subcutaneous tumors. Histologically, most of these subcutaneous tumors were mesenchymal tumors with spindle cells arranged in a storiform pattern, with sheets of histiocyte-like cells or pleomorphic giant cells. Electron microscopy showed mixture of fibroblastic cells, histiocytic cells and undifferentiated cells in these tumors. From these histological and electron microscopical findings, many of the tumors were diagnosed as malignant fibrous histiocytomas.

Animals↗

Development of thymic lymphomas by oral administration of N-nitroso-N-propylurea and establishment of transplantable lines of thymic lymphoma in F344 rats.

Forty-eight female F344/DuCrj rats were given a 400-ppm solution of N-nitroso-N-propylurea (CAS: 816-57-9) continuously in their drinking water. Thymic lymphomas were induced most frequently (85%) followed by duodenal tumors (48%). Sixteen tumors were examined by the immunofluorescence inhibition test for murine leukemia virus-related antigens; 15 were negative and the other was weakly positive. Twenty-six tumors were intraperitoneally and subcutaneously transplanted syngeneically; 25 (96%) were successfully transplanted intraperitoneally and 24 (92%) subcutaneously. The serial intraperitoneal transplantation was continued, and 22 lines of transplantable lymphoma in an ascites form were established. In almost all tumor lines, tumor cells took in a high percentage of recipient rats and caused the death of the recipients within 12-23 days. The thymus, liver, spleen, greater omentum, and lymph nodes were frequently invaded by transplanted tumor cells. The tumor lines were considered to be of T-cell lineage.

Administration, Oral↗

Spontaneous tumors of the nervous system and associated organs and/or tissues in rats.

Spontaneous tumors of the nervous system and associated organs and/or tissues in 346 male and 346 female F344/DuCrj rats and 200 male and 177 female Slc:Wistar rats were examined. The main neurogenic tumors observed were gliomas and neurinomas, which were detected in both strains of rats. Out of 7 gliomas, 6 were found in the brain and 1 in the spinal cord, and out of 4 neurinomas, 2 were in the trigeminal nerves and the other 2 were in the spinal nerves. In addition, other types of tumors (2 granular cell tumors in the brain, 1 pinealoma, 3 ganglioneuromas in the adrenal gland, 1 undifferentiated carcinoma in the nasal cavity and 1 chordoma in the posterior neck region) were observed.

Animals↗

Morphologic characteristics of thymic lymphomas induced by N-nitroso-N-propylurea in F344 rats.

Eighty-two thymic tumors induced by N-nitroso-N-propylurea in inbred F344/DuCrj rats were examined by light and electron microscopy. These tumors were diagnosed as malignant lymphomas and classified according to light microscopic features into three types: 1) lymphoblastic (57%), 2) large cell (32%), and 3) pleomorphic (11%). Electron microscopy revealed no epithelial cells in all 82 malignant lymphomas, except for 2, in which one sheet of epithelial cells was found under the capsule. This finding confirmed that all of these thymic tumors were malignant lymphomas, not thymomas. The tumors of the lymphoblastic and large cell types consisted of lymphoid cells with a few macrophages. Lymphoid cells of the lymphoblastic type were medium sized and contained a moderate amount of polyribosomes and a few clustered dense bodies; cells of the large cell type were much larger than those of the lymphoblastic type and contained many more polyribosomes and larger nucleoli. The tumors of the pleomorphic type consisted of lymphoid cells with severely infolded nuclei and interdigitating reticulum cells that were thought to be nonneoplastic in nature. No viral particle was found in these cells among the three types of thymic lymphomas.

Animals↗

Carcinogenicity of low doses of N-ethyl-N-nitrosourea in F344 rats; a dose-response study.

The threshold level of minimum carcinogenic dose of N-ethyl-N-nitrosourea (ENU) and the effect of dose on organ specificity were examined by continuous oral administration to both sexes of F344 rats of low doses of ENU at four concentrations (0.3, 1, 3 and 10 ppm) in the drinking water. ENU at 10 ppm selectively induced neurogenic tumors and tumors of the digestive tract, including duodenal tumors. Even at lower doses it enhanced the spontaneous development of some other tumors. A high dose of ENU (400 ppm) was previously found to induce duodenal tumors selectively. These results indicate that the organ specificity of ENU is influenced by the dose and that ENU has multi-potent carcinogenic activity in many organs and/or tissues. In this study, some specific tumors, such as those of the nervous system and digestive tract, seemed to require a minimum carcinogenic level of ENU (10 ppm) for their appearance. However, it seems that ENU is carcinogenic at much lower dose levels than 10 ppm because ENU enhanced the spontaneous development of some other tumors in many experimental groups. The so-called virtually safe doses inducing these specific tumors at a risk level of 10(-6) were calculated.

Animals↗

Induction of tumors in the small intestine and mammary gland of female Donryu rats by continuous oral administration of N-carboxymethyl-N-nitrosourea.

The carcinogenicity of N-carboxymethyl-N-nitrosourea (CMNU), a naturally occurring N-nitroso compound, was tested in female Donryu rats. Four groups of female Donryu rats were given 400, 200, 100, or 0 ppm of CMNU solution continuously as drinking water. The incidence of tumors was highest and the mean survival time shortest in the 400 ppm group. A dose-effect relationship was observed in the tumor incidence and the mean survival time and the incidences of tumors in all experimental groups were significantly different from those in the control group. In the 400 ppm group, tumors were detected most frequently in the small intestine, followed by the mammary gland. In contrast, most tumors were observed in the mammary gland in the other two experimental groups, although dose-dependent induction of tumors of the small intestine was also detected in these two groups. The organ specificity of CMNU is compared with that of other N-alkyl-N-nitrosourea derivatives.

Animals↗

Carcinogenicity study of ammonia-process caramel in F344 rats.

The carcinogenicity of ammonia-process caramel, a food colouring, was examined in F344 rats. Caramel was dissolved in distilled water at levels of 0, 1 and 4% and groups of 50 male and 50 female rats were given 20-25 ml of one of these solutions/rat/day as their drinking water for 2 yr. There were no significant differences between the total incidences of tumours or mean survival times of control and experimental groups. A variety of tumours developed in all groups including the control group, and no dose-related effects were found either in the incidence or induction time of tumours in the various organs and tissues except in the pituitary gland of males, in which the incidence of tumours in males given 4% caramel solution was significantly higher than that in controls. Pituitary tumours are among the most common spontaneous tumours in ageing rats of this strain and have a variable incidence. In addition, almost all pituitary tumours detected in males given the 4% solution were microscopic tumours, and there was no significant difference between controls and treated groups in the incidence of hyperplasia or pre-neoplastic lesions in the pituitary gland. These results indicate that the significantly higher incidence of pituitary tumours in males given the 4% caramel solution was not related to caramel administration, but could be explained by the variability of the incidence of spontaneous pituitary tumours. Thus it is concluded that under these experimental conditions ammonia-process caramel was not carcinogenic in F344 rats.

Age Factors↗

Induction of angiogenic tumors in the duodenum of female Donryu rats by continuous oral administration of N-isobutyl-N-nitrosourea.

Four groups of female Donryu rats were continuously given 400, 200, 100 or 0 ppm N-isobutyl-N-nitrosourea (iso-BNU) in their drinking water, and were examined for the development of tumors. The incidence of digestive tract tumors was 25/28 (89%), 14/24 (58%), 6/25 (24%) and 0/17 (0%), in the 400, 200, 100 and 0 ppm groups, respectively. The predominant type of digestive tract tumor was angiogenic, and a few were of the epithelial type. A dose-effect relationship was clearly demonstrated not only in the incidence of digestive tract tumors but also in the average survival period of rats with these tumors.

Administration, Oral↗

Spontaneous tumors in F-344/DuCrj rats.

Spontaneous tumors in 296 male and 297 female F-34/DuCrj rats used as control groups in six carcinogenicity tests were tabulated and evaluated. In males the most frequent tumors were testicular interstitial cell tumors, followed by mammary fibromas and fibroadenomas, mononuclear cell leukemias, pheochromocytomas, C-cell adenomas of the thyroid, pituitary adenomas, preputial adenomas, neoplastic nodules of the liver, and lung adenomas. In contrast, in females pituitary adenomas, uterine endometrial stromal polyps, mammary fibroadenomas, mononuclear cell leukemias and C-cell adenomas were the most common. Various other tumors of almost all other organs and/or tissues were found, although their incidences were low. Variability in the rates of incidence in some tumors was observed in different control groups.

Age Factors↗

Carcinogenicity of N-alkyl-N-(acetoxymethyl)nitrosamines after subcutaneous injections in F-344 rats.

As model compounds for metabolically activated N,N-dialkylnitrosamines, five N-alkyl-N-(acetoxymethyl)nitrosamines were synthesized and their carcinogenicity was tested in F-344 rats of both sexes. Compounds used in this study are N-methyl-(MAMN), N-ethyl-(EAMN), N-propyl-(PAMN), N-butyl-(BAMN), and N-isobutyl-N-(acetoxymethyl)nitrosamines (i-BAMN). All chemicals were dissolved in olive oil and rats received 10 weekly subcutaneous injections of these chemicals (10 X 5 mg MAMN or equimolar amounts of other chemicals) at the interscapular region. Subcutaneous tumors were detected in many rats of all groups treated with the chemicals, although no tumor was detected in the control group. Lung and/or thyroid tumors were also observed in many rats in the experimental groups. The incidence of subcutaneous tumors was highest in EAMN, followed in order by MAMN, PAMN, BAMN, and i-BAMN. On the contrary, the incidence of lung and thyroid tumors was highest in MAMN and decreased as the length of the alkyl chain of the chemicals increased. Histologically, almost all subcutaneous tumors were malignant fibrous histiocytomas. The results indicate that the chemicals possess systemic as well as local carcinogenicity in F-344 rats. The potent carcinogenic effects at the injection site of the alpha-acetoxy nitrosamines, coupled with their direct mutagenic activity reported previously, support the notion that these derivatives are useful as models for the ultimate form in the metabolic activation of N,N-dialkylnitrosamines.

Animals↗

Carcinogenicity studies of sodium nitrite and sodium nitrate in F-344 rats.

The carcinogenicity of sodium and of sodium nitrate was examined in F-344 rats. Sodium nitrite was administered in the drinking-water for 2 yr at levels of 0.125 or 0.25%. Sodium nitrate was given in the diet at levels 2.5 or 5%. A variety of tumours occurred in all groups including the controls. The only significant difference between treated and control groups in the total number of tumours detected in either of the studies was a significant decrease in tumour incidence in the high-dose females given nitrite compared with controls. There was no positive dose-response relationship either in the incidence or in the induction time of tumours in either of the studies. The only significant result was a reduction in the incidence of mononuclear cell leukaemias in the experimental groups in both studies. It is concluded that sodium nitrite and sodium nitrate did not exert a carcinogenic effect that could be detected under the conditions of this study in which the animals showed a high incidence of spontaneous tumours.

Animals↗