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Biomedical subjects

S Odashima

Publications and source records attributed to S Odashima.

At least 73 records · Page 4Linked to original sources

[An approach to prolongation of survival rate in tumor bearing mice using 5-fluorouracil in combination with various kinds of herb medicine].

The effect of 5-fluorouracil (5-FU) in combination with herb medicine on the prolongation of survival rate in tumor bearing mice was studied. 5-FU directly inhibited the growth of cancer cells in vitro. However, the herb medicines used in this experiment showed neither an inhibitory effect on the growth of cancer cells nor prevention of inhibitory effect of 5-FU on the growth of cancer cells. 5-FU in combination with various kinds of herb medicine prolonged the survival time of tumor bearing mice. 5-FU in combination with shosaiko-toh was most effective; its increase of life span (ILS) was by 56%. However, mitomycin C in combination with shosaiko-toh was not associated with the prolongation of the survival rate of tumor bearing mice. The long-term administration of 5-FU to rats resulted in decrease in body weight, food intake, and white blood cell count, and these symptoms were improved when 5-FU was used in combination with shosaiko-toh. However, the increase in A/G ratio due to a decrease in the serum globulin fraction and marked atrophy of the thymus were not improved even when shosaiko-toh was combined with 5-FU.

Animals↗

Carcinogenicity of potassium bromate administered orally to F344 rats.

The carcinogenicity of potassium bromate, a food additive and a neutralizer in permanent waving, was tested by adding it to the drinking water of F344 rats for 110 weeks. Groups of 53 males and 53 females, each, were given solutions of 500 or 250 ppm of potassium bromate or distilled water. A concentration of 500 ppm markedly inhibited an increase of body weight of male rats. The mean survival time was shortest for males given 500 ppm (88.1 +/- 18.1 wk); the survival times of other groups were 101-104 weeks. The percentage survival in week 104 was relatively high in all groups, and it was 77.4% for males and 66.0% for females in the control group. High incidences of renal cell tumors (in males and females given 500 or 250 ppm) and mesotheliomas of the peritoneum (in males given 500 ppm) were observed. The incidences of these tumors in test groups were significantly higher than those in controls (P less than .001). It was concluded that, when orally administered under the conditions of this experiment, potassium bromate was carcinogenic to F344 rats.

Adenocarcinoma↗

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↗

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↗

Protective effect of saikosaponin-d isolated from Bupleurum falcatum L. on CCl4-induced liver injury in the rat.

The effects of saikosaponin-d extracted from the roots of Bupleurum falcatum L. on carbon tetrachloride-induced hepatic injury were studied in rats. Pretreatment with saikosaponin-d produced a remarkable inhibitory action on acute hepatic injury by CCl4. A significant inhibition of lipid peroxidation induced by an acute dose of CCl4 in the liver of rats pre-treated with saikosaponin-d was also noted. Continuous injection of CCl4 caused liver cirrhosis in rats but the severity of cirrhosis was reduced in rats treated simultaneously with CCl4 and saikosaponin-d.

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↗

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↗

An organ culture method for glandular stomach of new born rat.

An organ culture system has been developed for he long-term maintenance of the glandular stomach of new born Wistar rats. The explants from glandular stomach were cultured on Millipore filter in an organ culture dish with various media consisting of sera, buffers and additives under different gas phases of oxygen, carbon dioxide and nitrogen at 37 or 24 degrees C. The culture condition was evaluated by histological examination of explants and was divided into Grade (+++), (++), (+) and (-) depending upon the morphology and growth of the mucosal epithelium. D-MEM plus fetal calf serum (20%) supplemented with hydrocortisone (10 microgram/ml) or dexamethasone (5 microgram/ml) buffered with sodium bicarbonate and Hepes under a gas phase of O2 (95%)+CO2(5%) or (2(45%)+CO2(5%)+N2(50%) at 37 degrees C showed the best result. Other supplements tested, such as insulin, ascorbic acid and ferrous sulfate were ineffective. Addition of hydrocortisone or dexamethasone was similarly effective in serum-free media. Isologous rat serum had no advantage over fetal calf serum. Transplantation and autoradiography revealed the viability of the explants up to 35 days in vitro.

Animals↗

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↗

Overview: N-nitroso compounds as carcinogens for experimental animals and man.

A number of papers relating N-nitroso compounds as carcinogens for experimental animals and man was reviewed. These summerized in (1) early works, (2) amines and sodium nitrite, (3) disease models, (4) species susceptible to nitrosamines, (5) target organs, (6) strain specificity, (7) individual specificity and (8) minimum carcinogenic dose. Through these literature references and the results of animal experiments in the author's own laboratory on various acylated N-nitroso compounds, the possibility that various preformed nitrosamines in the environment, as well as those which are formed in our body, can cause tumors of various organs in human body is highly suggested.

Amines↗

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↗