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S Odashima

Publications and source records attributed to S Odashima.

At least 109 records · Page 6Linked to original sources

Chromosome tests with 134 compounds on Chinese hamster cells in vitro--a screening for chemical carcinogens.

Chromosomal aberration tests in vitro were carried out on Chinese hamster cells grown in culture with various chemicals, including carcinogenic N-nitroso compounds and their related derivatives, food additives, medical drugs, pesticides and other chemicals commonly used in laboratories or industries. Sixty-three of the 134 chemicals gave negative results in our test system even with doses at which the cell growth was markedly inhibited. Nearly all compounds known to be mutagenic in bacteria were also positive in our tests. Both urethane and diethylstilbestrol were positive, even though they are known to be carcinogenic but not mutagenic in bacteria. Compounds such as N-alkyl-N'-nitroguanidines, barbital, sodium benzoate, saccharin sodium, sodium nitrite, sodium nitrate and 4-aminoquinoline-1-oxide were positive in our chromosome tests, but they have not been conclusively tested for their carcinogenicity.

Animals↗

Induction of tumours by administration of N-dibutylnitrosamine and derivatives to infant mice.

Pulse doses of N-dibutylnitrosamine(DBN), N-butyl-N-(4-hydroxybutyl)nitrosamine(BBN) and N-butyl-N-(3carboxypropyl)nitrosamine(BCPN) suspended in 1% gelatin, were administered s.c. to infant CDF1 mice, and the experiment terminated at one year of age. Tumours were induced in lungs and liver. The incidences of lung adenomas were 73-95% in all treated mice, with no sex differences. Hepatocellular adenomas and a carcinoma were found with an incidence of 81% (21/26) in DBN, 59% (13/22) in BBN, and 32% (9/28) in BCPN-treated males and the incidence was 23% (5/22) in DBN-treated females. Only one papilloma of the fore-stomach was induced in mice treated with DBN. These results indicated that the s.c. administration of DBN, BBN, and BCPN induced tumours of the lung and liver, but no tumours of the urinary bladder, under these experimental conditions. The carcinogenic effect on mice at the treated dose level was DBN greater than BBN greater than BCPN.

Adenoma↗

Antitumor effect of 1,1'-polymethylene-bis (1-nitrosourea) and related compounds.

Polymethylene-bis(1-nitrosourea), polymethylene-bis(1-nitroso-3-nitroguanidine), and polymethylene-bis(1-nitroso-p-toluenesulfonamide) derivatives were tested for antitumor effect against rat ascites hepatoma AH-13 and mouse leukemia L-1210. Bisnitrosoureas were effective against AH-13 and L-1210, bisnitrosoguanidines were effective against AH-13 alone, and bisnitrosotoluene-sulfonamides were ineffective against both tumor lines. Of all these compounds, 1,1'-ethylene-bis(1-nitrosourea) (EBNU) was the most effective. The antitumor effect of EBNU was compared with that of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Intraperitoneal administration of EBNU according to the schedule, day 1, days 1 and 5, and days 1, 5, and 9 after intraperitoneal inoculation of L-1210 showed marked prolongation of host survival, although the effective doses used were a few times higher than those used in BCNU to obtain a similar effect. The minimum effective dose (MED) of EBNU on AH-13 cells was estimated as 1 mg/kg, which was 10 times less than that of BCNU, suggesting that EBNU was more effective than BCNU against AH-13.

Animals↗

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↗

Transplacental carcinogenesis and chemical determination of 1-butyl-1-nitrosourea in stomach content after simultaneous oral administration of 1-butylurea and sodium nitrite to ACI/N rats.

Solutions of 100 mg/kg 1-butylurea and 50 mg/kg sodium nitrite were administered daily by a stomach tube to pregnant ACI/N rats from the 13th to 21st day of gestation. Neurogenous tumors were induced in their offspring. The incidence of tumours and mean survival time of rats with nervous tumours were 64% (23/36) and 309 (189672) days respectively. Localization and histological findings of the nervous tumors were similar to those observed previously in rats whose mothers received 1-butyl-1-nitrosourea (BNU) during pregnancy. Neurogenous tumors did not develop in the offspring of the mothers that received 100 mg/kg of 1-butylurea alone in the same manner. In several rats of both group, a few spontaneous tumors of the testis, pituitary gland, urinary bladder, uterus, and colon were detected. In vivo formation BNU in stomach content after intubation of 1-butylurea and sodium nitrite was determined. BNU was detected in the stomach content at levels of 25 ppm at 30 min and 23 ppm at 60 min after administration. The concentration of BNU in the stomach content corresponded to 48.3 and 29.2 microng/rat, respectively.

Animals↗

Induction of tumors in the stomach and nervous system of the ACI/N rat by continuous oral administration of 1-methyl-3-acetyl-1-nitrosourea.

Three groups of ACI/N rats of both sexes received continuous administration of 66 (Group I), 30 Group II), or 13(Group III) ppm solution of 1-methyl-3-acetyl-1-nitrosourea (Ac-MNU) in their drinking water. Tumors were found most frequently in the stomach and nervous system. The former was more frequently found in the male than in the female. The incidence was highest in males of Group II, 28/30 (93%), and lowest in females of Group I, 4/30 (13%). Histologically, all epithelial tumors of the stomach were benign adenomas except 5 adenocarcinomas. Neurogenous tumors were more frequently seen in the female than in the male. The incidence was highest in females of Group I, 29/30 (97%), and lowest in males of Group III, 6/28 (21%). The tumors were predominant in the central nervous system, especially in the hemispheres. Transplantation studies were done in some of these tumors. Although gastric tumors failed to get positive transplantation, all the neurogenous tumors transplanted were positive.

Adenoma↗

Studies with mature rat hepatocytes in monolayer culture. I. Propagation of isolated hepatocytes, morphological and biochemical in culture.

Differentiated cells have been established in monolayer culture from adult rat liver and their ultrastructural and biochemical features characterized after 20-30 generations. Hepatocytes were isolated by enzyme perfusion of the liver followed by treatment with papain, which allowed cultures to be established more readily and to be cloned at an early stage. Ultrastructural studies indicated that the cells were derived largely from hepatic parenchymal cells. The cells showed structural modifications during primary culture but were stable thereafter. The cultured cells retained some differentiated functions unique to liver cells, including the synthesis of ornithine form arginine and the secretion of serum proteins, albumin, chi- and beta-globulins.

Animals↗

Leukemias and vaginal tumors induced in female Donryu rats by continuous administration of 1-butyl-3,3-dimethyl-1-nitrosourea in the drinking water.

Three groups of Donryu rats, each consisting of 36 females, were continuously given solutions of 1-butyl-3,3-dimethyl-1-nitrosourea as drinking water (400 ppm for group A, 200 ppm for group B 100 ppm for group C). Of the 100 rats that survived at least 122 experimental days, 64 developed leukemia and 38 had vaginal tumors. Leukemias were preponderant in animals of groups A and B; vaginal tumors appeared in group C.

Animals↗

Tumors of the upper digestive tract of ACI/N rats given N-propyl-N-nitrosourethan in the drinking water.

Three groups of ACI/N rats of both sexes were given 400, 200, or 100 ppm of N-propyl-N-nitrosourethan (PNUR) continuously in the drinking water. The incidence of tumors in the upper digestive tract was 100% in all 3 groups. These tumors were observed most frequently in the forestomach, followed by the esophagus, oral cavity, and pharynx. Histologically, all the tumors were papillomas or squamous cell carcinomas. A few tumors were detected in the small intestine and glandular stomach. The study on morphogenesis of squamous cell carcinomas arising from the upper digestive tract indicates that the majority of tumors of the esophagus and forestomach may pass through acanthosis or hyperkeratosis, leukokeratosis, and papilloma, and finally develop into invasive squamous cell carcinoma, but many carcinomas of the oral cavity and pharnyx, especially the tongue, may develop without passing through a papillomatous stage.

Animals↗

Rapid and selective induction of erythroleukemia in female Donryu rats by continuous oral administration of 1-ethyl-1-nitrosourea.

Three groups of female Donryu rats were given continuously 1-ethyl-1-nitrosourea, 400, 200, or 100 mg/liter, in their drinking water. Leukemias developed in 94 of 104 (92%) rats surviving more than 6 experimental weeks. Of the leukemias, the erythroleukemias were induced most frequently, rapidly, and selectively. Other types of leukemias were found in a few rats of the high-dose group and, in some cases, in rats of the low-dose group. Tumors were also induced in the digestive tract, mammary glands, ear duct, and other organs, but their incidences were lower than 24%.

Administration, Oral↗

Tumor induction by a single subcutaneous injection of sterigmatocystin in newborn mice.

Sterigmatocystin, a mycotoxin produced by Aspergillus versicolor, Aspergillus sydowi, Aspergillus nidulans, and a species of Bipolaris, was given to newborn BALB/c X DBA/2F1 (hereafter referred to as CD2F1) mice by a single s.c. administration in 1% gelatin suspension. In an acute toxicity study, the maximum tolerated dose of sterigmatocystin was 5 mug/g body weight. In a chronic study, a single s.c. injection of 5, 1, or 0.5 mug/g body weight gave rise to high incidences of lung and liver adenomas when the animals were killed at the end of 1 year. The incidence of both tumors in mice at the dose of 5 mug/g body weight was statistically significant, and the incidences of lung tumor in female mice and of liver tumor in male mice at the dose of 1 mug/g body weight were also statistically significant, compared with tumors in control mice. Other tumors also were induced in treated mice (two malignant lymphomas and one adenoma of the submaxillary gland), in contrast to a zero incidence in vehicle control mice. These results confirm that a small quantity of sterigmatocystin induces tumors of lung and liver and that the dose of sterigmatocystin is related to the incidence of tumors in mice.

Adenoma↗

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↗

Spontaneous tumors in ACI/N rats.

One hundred ninety-five spontaneous tumors, developing in 55 male and 209 female ACI/N rats in 169 weeks, were studied. The incidence was 56% (31/55) in males and 52% (108/209) in females; their average survival time was 113 and 108 weeks, respectively. These neoplasms were found in all organ systems except those of the sensory and locomotor systems. In the males, interstitial cell tumors of the testis (45.5%, 25/55) were most frequent, followed by those in the adrenal (16.4%, 9/55) and pituitary glands (5.5%, 3/55), skin (5.5%, 3/55), and urinary bladder (3.6%, 2/55). In female rats, tumors of the pituitary gland (21.1%, 44/209), uterus (12.9%, 27/209), mammary gland (11.1%, 23/209), adrenal gland (5.7%, 12/209), urinary bladder (4.8%, 10/209), thymus and lymph nodes (4.3%, 9/209), subcutaneous tissues (1.4%, 3/209), heart (1.4%, 3/209), vagina (1.0%, 2/209), and salivary gland (1.0%, 2/209) were detected. In addition, tumors of the glandular stomach, small intestine, spleen, trachea, lacrymal gland, ovary, brain, kidney, thyroid, and bone marrow were detected in 1 female each, and those of the small intestine, spleen, lung, and peritoneum in 1 male rat each. Only 6 adenocarcinomas of the uterus, 3 lymphatic leukemias, 1 cortical carcinoma, and 1 mesothelioma of 195 tumors observed in the present studies metastasized to remote organs.

Adrenal Gland Neoplasms↗

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↗

Induction of tumors of the nervous system in the ACI/N rat with 1-butyl-1-nitrosourea administered transplacentally, neonatally, or via maternal milk.

1-Butyl-1-nitrosourea (BNU), a strong leukemogen for rats and mice, was administered prenatally, neonatally, and to sucklings via maternal milk in the ACI/N rats. A high incidence of neurogeneous tumor was obtained in the offspring of the mother rats that received 3 subcutaneous injections of 10 mg/rat of BNU at the late stage of pregnancy and also in the animals that received one subcutaneous injection of 100 mg/kg of BNU within 24 hr after birth. Though in low incidence, the tumors also developed in the offspring of the mothers that received the BNU treatment at the middle stage of their pregnancy or in the rats that were nursed by the mother rats which received 3 subcutaneous injections of 300 mg/kg of BNU during lactation. Contrary to expectations, leukemia developed in only one rat of all the offspring of the mother animals that received the BNU treatment during their pregnancy.

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↗