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Biomedical subjects

T Ogiu

Publications and source records attributed to T Ogiu.

At least 73 records · Page 4Linked to original sources

Induction of rat leukemias and thymic lymphoma by N-nitrosoureas.

Some of the recent advances in experimental research on leukemogenesis have been due to the use of various N-nitrosoureas. Specifically, N-ethyl-, N-n-propyl-, N-n-butyl-, and N-n-butyl-N',N'-dimethyl-N-nitrosoureas have been found to be effective for inducing leukemias in rats. The induced leukemias are divided into four major types; myeloblastic, myelocytic, erythroblastic, and lymphoblastic, and each type is hematologically and pathologically characteristic. Four possible pathways for the induction process of leukemia by N-nitrosoureas are proposed and discussed. 1) Normal hematopoietic cell(s) mutate directly into leukemic cell(s) by the direct action of N-nitrosourea. 2) Hematopoietic cell(s) recover from chemically or physiologically induced cytotoxic effects and undergo proliferation into leukemic cell(s) by secondary N-nitrosourea action. 3) Bone marrow cell(s) are altered by chemical or physical agents and exhibit genetic instability to become leukemic cell(s) by secondary N-nitrosourea action. 4) The bone marrow cells upon interaction with chemical or physical agents become altered cells, which may undergo intensive clonal proliferation. These proliferating cells may subsequently interact with additional N-nitrosourea to develop into leukemic cell(s). In addition, the immunosuppressive state of the host, various growth factors, and promotors may also act on the newly induced leukemic cell(s) to produce and apparent leukemia. Experiments on rat thymic lymphoma are also briefly reviewed.

Animals↗

Carcinogenicity of alpha-oxidized nitrosamines (alpha-acyloxy, alpha-hydroperoxy, and alpha-oxo nitrosamines) in F-344 rats.

The carcinogenicity of eleven alpha-oxidized nitrosamines (alpha-acyloxy, alpha-hydroperoxy and alpha-oxo nitrosamines) was tested in F-344 rats. All chemicals were dissolved in olive oil and rats received 10 weekly subcutaneous injections of these chemicals (10 x 5 mg/kg of N-methyl-N-(acetoxymethyl) nitrosamine or equimolar amounts of the other chemicals) at the interscapular region. Subcutaneous tumours were detected in many rats of all groups treated with the chemicals, although no tumour was detected at the injection site in the control group. Lung and thyroid tumours were also observed in many rats of the treated groups, especially those injected with N-alkyl-N-(acetoxymethyl)nitrosamines. Many other tumours developed in the experimental groups, but it is not certain that they were related to the treatment with the chemicals. The results indicate that the chemicals possess local as well as systemic carcinogenicity in F-344 rats. The potent carcinogenic effects at the injection site of the alpha-oxidized nitrosamines, coupled with their direct mutagenic activity, suggest that these derivatives are useful models for the ultimate form of the metabolically activated nitrosamines.

Animals↗

Sandhoff disease.

An autopsy case of Sandhoff disease in a 2-year-old boy is reported. Diagnosis was established by enzyme assay, which demonstrated total deficiency of hexosaminidase in the serum. Histochemical examination, using hematoxylin-eosin (H & E) and Luxol fast blue (LFB) stain, showed accumulation of LFB-positive material not only in cells of the cerebrum, cerebellum, spinal cord, and peripheral nervous system, but also in reticuloendothelial cells of the lymph nodes, spleen, thymus, and liver, in podocytes of renal glomeruli, in all types of renal tubular cells, in endothelial cells of small vessels, in fibroblasts, and in epithelial cells of the epididymis and ductus deferens. Electron microscopic examination showed that these deposits contained electrondense membranous bodies. Lipid analysis demonstrated a marked elevation of ganglioside GM2 and its asialo derivative in the brain and liver. Accumulation of globoside was found in the liver, kidney, and spleen. There was complete absence of hexosaminidase in the brain and liver.

Brain↗

Mammary tumorigenic effect of a new nitrosourea, 1,3-dibutyl-l-nitrosourea (B-BNU), in female Donryu rats.

Four groups (groups 1-4) of female Donryu rats were given continuously 400, 200, 100, or 0 ppm solution of 1,3-dibutyl-l-nitrosourea (B-BNU) as their drinking water, and were studied for the development of tumors. The incidence of mammary tumors was 15/19 (79%), 20/24 (83%), 21/26 (81%), and 8/25 (32%) in groups 1, 2, 3, and 4, respectively. In addition, hematopoietic neoplasms, uterine tumors, and vaginal tumors developed in 13, 11, and six rats, respectively in 69 treated rats. Other tumors were infrequent.

Animals↗

Induction of duodenal tumors in F344 rats by continuous oral administration of N-ethyl-N-nitrosourea.

Forty male and 40 female inbred F344 rats were given a solution of 400 mg N-ethyl-N-nitrosourea/liter in their drinking water. Digestive tract tumors were induced in 32 males (an incidence rate of 80%) and in 28 females (an incidence rate of 70%). Among these digestive tract neoplasms, duodenal tumors occurred most frequently. Most were of the epithelial type, such as adenoma or adenocarcinoma. Tumors in hematopoletic organs were also found in 15 males (38% incidence) and in 17 females (43% incidence).

Animals↗

Induction of digestive tract tumors and leukemias in Donryu rats by administration of 1-amyl-1-nitrosourea in drinking water.

The effects of administration of 1-amyl-1-nitrosourea (ANU) at doses of 400, 200, 100 and 0 ppm in the drinking water to Donryu rats of both sexes were studied. Tumors developed in 166/205 (81%) rats that received ANU, as compared with 9/34 (27%) control rats. The incidence of digestive tract tumors was highest (76%), followed by hematopoietic tissue (11%) and liver (9%) tumors. In females, mammary tumors were also found. There appeared to be a dose-response relationship among the 3 treated groups as regards the incidence of tumors of the hematopoietic tissues and the average survival time.

Animals↗

Induction of duodenal-tumors and thymomas in Fischer rats by continuous oral administration of 1-propyl-1-nitrosourea.

Male and female F344/DuCrj rats were given 400 ppm solution of 1-propyl-1-nitrosourea continuously in their drinking water. The incidence of digestive tract tumors was as high as 32/36 (89%) and 33/39 (85%) in male and female rats, respectively. Among these, duodenal tumors were induced most frequently, and most of them were adenocarcinoma followed by adenomas and hemangiogenic tumors. Thymomas were found in 27 (75%) males and 14 (36%) females. The lymphocytic type thymoma was the most frequent, and epithelial or mixed types were found only in 8 females. Other tumors induced were mainly in the ear ducts and lung, and the incidence was less than 13%.

Adenocarcinoma↗

Growth of intraperitoneally transplanted ascites hepatoma, AH39 cells, in the area of gelatin sponge inoculation into the abdominal wall of Donryu rats.

A piece of gelatin sponge was inoculated submesothelialy in the abdominal wall of female Donryu rats, and 1, 2, 4, 7, 14, or 21 days later, 1 x 10(5) cells of ascites hepatoma AH39 were intraperitoneally transplanted. Tumor cells were detected in the area of gelatin sponge inoculation in each group 2 to 5 days after the transplantation. Generally, the number of rats in which tumor cells were detected was larger in those transplanted with tumor cells within a short period after the gelatin sponge inoculation. Changes in the area of gelatin sponge inoculation and nontreated area in the rats which received intraperitoneal transplantation of the tumor cells on the 1st day after gelatin sponge inoculation were studied. Tumor cells were detected in the area of gelatin sponge inoculation as early as 2 days after the tumor transplantation, whereas they were detected on the 14th day in nontreated areas. Tumor detection was preceded by inflammatory reaction in both cases.

Abdominal Muscles↗

Induction of tumors of peripheral nervous system in female Donryu rats by continuous oral administration of 1-methyl-1-nitrosourea.

Groups 1, 2, and 3 of female Donryu rats were given continuously 400, 200, or 100 ppm solution of 1-methyl-1-nitrosourea (MNU) as their drinking water. The incidence of neurogenic tumors was 12/27 (44%), 39/33 (91%), and 33/36 (92%) in Groups 1, 2, and 3, respectively. Among the neurogenic tumors, neurinomas developing from the spinal nerve roots were the most frequent. In addition, tumors of the digestive tract were found in 12, 1, and 2 rats in Groups 1, 2, and 3, respectively, and tumors in hematopoietic tissues developed in 6 rats. Tumors in other organs were infrequent.

Administration, Oral↗

Induction of tumors in female Donryu rats by a single administration of 1-propyl-1-nitrosourea.

Three groups of female Donryu rats were given a single gastric intubation of 800, 400, or 200 mg/kg body weight of 1-propyl-1-nitrosourea and one group of female Donryu rats was given a single subcutaneous injection of 1-propyl-1-nitrosourea. The incidence of tumors was highest for mammary tumors and leukemia, and next for tumors of the ovary, thyroid, and adrenal glands, and in the digestive tract in rats given the chemical by oral administration. There were also scattered tumors in various other organs. Mammary and subcutaneous tumors were found in some rats given a subcutaneous injection of 1-propyl-1-nitrosourea.

Animals↗

Leukemias induced by 1-butyl- and 1-propyl-1-nitrosoureas in the rat.

The leukemogenic effect of 1-propyl- and 1-butyl-1-nitrosourea (PNU and BNU) was studied in Donryu and Sprague-Dawley rats, which received the chemical in their drinking water. BNU produced leukemia in 42 out of 46 (91%) of the Donryu rats, and the majority of the induced leukemia were myeloblastic type. In the Sprague-Dawley rats, the incidence of leukemia was 70% (47/67), of which 37%(13/35) were myelocytic leukemia, although the development of myeloblastic leukemia was still predominant (54%, 19/35). The leukemogenic activity of PNU was slightly lower than that of BNU; it produced leukemia in 64% (61/95) of the Donryu rats. The predominant type of induced leukemia was myelocytic leukemia (59%, 36/61). Therefore, it was demonstrated through the series of experiments using BNU and PNU that the strength of leukemogenic activity has a close relationship to the types of leukemia induced in animals. Both BNU and PNU, however, provide excellent disease models of myelogeneous leukemia in the human being.

Animals↗

Induction of Leukemias and digestive tract tumors in Donryu rats by 1-propyl-1-nitrosourea.

Three groups of female Donryu rats were continuously given 600, 300, or 150 ppm solution of 1-propyl-1-nitrosourea in their drinking water. Leukemias developed in 62 of 109 (57%) rats surviving for more than 17 weeks and tumors developed in the digestive tracts of 31 (28%) animals. Of the leukemias, the differentiated myelocytic type was the most frequent, followed by myeloblastic leukemia and erythroleukemia. Tumors in the digestive tract, predominantly in the glandular stomach and duodenum, were both epithelial and nonepithelial. The other induced tumors were mainly in the mammary glands, ear ducts, and thymus, though the incidence was less than 15%.

Animals↗

Carcinogenic effect of 1-butyl-1-nitrosourea on female Sprague-Dawley rats.

Carcinogenic effect of a single oral administration of 300 or 200 mg/kg body weight of 1-butyl-1-nitrosourea (BNU) and continuous oral administration of 400 ppm solution of BNU in the drinking water for 5, 10, 15, and 20 weeks to female SD rats was studied. In addition, the number of spleen cells capable of forming plaques (PFC) against primary immunization with sheep red blood cells was investigated in various stages of the animal experiments. With a single oral administration of BNU, tumors developed in 31/50 (62%) rats between the 25th and 75th week. They were most frequently seen in the mammary gland (40%), followed by the stomach (10%), kidneys (8%), and ovary (8%). Leukemia was found in 8%. No dose-effect relationship was observed in these 2 experimental groups. On the other hand, tumors developed in 67/77 (88%) of the rats that received BNU in their drinking water. The incidence of tumors was highest in leukemia (61%), followed by mammary tumors (26%), intestinal tumors (12%), and ear duct tumors (8%). There was a dose-effect relationship among the 4 groups in the latent period and target organs for tumor development. Although the PFC count of the rats receiving BNU for 5 weeks recovered gradually to about 50% of the control level at the end of the 25th experimental week, it remained less than 10% of the control level for the whole experimental period in those receiving BNU longer than 10 weeks. Therefore, it was apparent that the tumors developed, proliferated, and finally killed the host rats in highly immunosuppressive state.

Adenocarcinoma, Papillary↗

Induction of ovarian tumors by heavy ion irradiation in B6C3F1 mice.

Six-week-old B6C3F1 mice were exposed to 0.439 Gy heavy ion irradiation as a 290 MeV/u carbon-ion beam (LET 10 keV/micron) at 2 cm from the upper proximal point of a spread Bragg beam and autopsied 13.5 months after the irradiation. In males total tumor incidences, mainly liver tumors, were 37.0% in irradiated group and 25.0% in control (P>0.05). In females the total tumor incidences were 32.3%, mainly ovarian tumors, in the irradiated group and 0% in the controls. These results indicate that heavy ion irradiation induces ovarian tumors in females but does not target any organ in males.

Adrenal Glands↗