Biomedical subjects
Publications and source records attributed to N Takamura.
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In order to ascertain the minimum induction time, minimum treatment period and total dose required for development of renal cell tumors, KBrO3 at a concentration of 500 ppm was administered in the drinking water to a total of 232 male F344 rats divided into 14 experimental groups and the development of tumors was examined by two different approaches. In a continued-treatment study, administration of KBrO3 was stopped at week 13, 26, 39, 52 or 104 and rats were immediately sacrificed for comparison with controls given distilled water (DW) alone. Renal cell adenomas were found as early as after 26 weeks of treatment with KBrO3. The yields of dysplastic foci, adenomas and adenocarcinomas of the kidney, follicular cell tumors of the thyroid and mesotheliomas of the peritoneum increased with treatment, the final incidences all being statistically significant after administration of KBrO3 for 104 weeks. To examine the effect of discontinued treatment, on the other hand, the rats were given KBrO3 for the first 13, 26, 39 or 52 weeks and were subsequently maintained on DW alone until sacrifice at week 104. The incidences of tumors in these groups were compared with that of a group continuously administered KBrO3 for 104 weeks. The yields of renal dysplastic foci, adenomas and adenocarcinomas in all discontinued-treatment groups were approximately equal to or even higher than those in the group given KBrO3 continuously for 104 weeks. It is concluded that, under the conditions of this study: the minimum induction time for the development of renal adenomas was 26 weeks and the minimum treatment period and total dose for the induction of renal adenomas and adenocarcinomas were 13 weeks and 4 g/kg, respectively, when the rats were maintained thereafter on DW for 2 years.
Nalidixic acid (NA), a drug used for the treatment of urinary-tract infections, was administered in the diet to groups of 51 male and 51 female CDF1 mice at concentrations of 0, 0.08 and 0.16% for 76 wk. All the surviving animals were killed at wk 85 after 9 wk on the basal diet. Survival of the treated male and female mice was similar to that of the corresponding controls. The body weights were slightly lower in high- and low-dose males and in high-dose females than in the controls. All groups showed relatively high incidences of tumours of the small intestine, lung and haematopoietic organs in both sexes, of the liver and Harderian gland in males and of the uterus in females. However, there were no statistically significant differences between NA-treated and control mice of either sex in the incidences of tumours in any organs. It was therefore concluded that, under the conditions of this study, NA showed no carcinogenic potential in either male or female CDF1 mice.
Dose-response studies on the carcinogenicity of potassium bromate (KBrO3), a food additive, were undertaken to examine its effects at low doses. A total of 148 6-week-old male inbred F344 rats were divided into 7 groups. They were given KBrO3 orally in their drinking water at doses of 500, 250, 125, 60, 30, 15, and 0 ppm for 104 weeks, at the end of which time all the surviving animals were autopsied and then examined histopathologically. Shortening of the survival times and marked inhibition of body weight increase were observed in a group given 500 ppm KBrO3. The combined incidences of renal adenocarcinomas and adenomas were significantly increased in rats treated with KBrO3 at doses of 500, 250, and 125 ppm in a dose-related manner. The dose-response curve showed a sigmoid appearance. The value for the virtually safe dose (VSD), calculated by the probit model, was 0.950 ppm KBrO3 at a risk level of 10(-6). However, significant increases in the occurrence of dysplastic foci of the kidney were found in groups at doses higher than 30 ppm KBrO3. The VSD value for the dysplastic foci estimated by the gamma-multi-hit model was 0.148 X 10(-3) ppm KBrO3 at a risk level of 10(-6). In a group tested with 500 ppm KBrO3, the combined incidences for follicular adenocarcinomas and adenomas of the thyroid and for mesotheliomas of the peritoneum were shown to be significantly increased.
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Dose-response studies were undertaken to investigate the enhancing activity of potassium bromate (KBrO3), a food additive, on renal tumorigenesis initiated by N-ethyl-N-hydroxyethylnitrosamine (EHEN). A total of 180 male 6-week-old F344 rats were divided into 12 groups. EHEN was given in the drinking water for the first 2 weeks at a concentration of 500 ppm for initiation of carcinogenesis. Thereafter, the rats were treated orally either with KBrO3 at a concentration of 500, 250, 125, 60, 30 or 15 ppm, or with potassium bromide (KBr) at a concentration of 1750 or 350 ppm for 24 weeks. The mean numbers of kidney dysplastic foci were significantly increased in a dose-related manner in rats treated with more than 30 ppm KBrO3. The mean number of renal cell tumors was significantly higher after treatment with KBrO3 at the highest concentration of 500 ppm. On the other hand, KBr had no effect. It was concluded that KBrO3 at doses higher than 30 ppm in the drinking water has an enhancing effect on renal tumorigenesis.
Six oxidizing chemicals were tested for promoting and complete carcinogenic activities in skin carcinogenesis using female Sencar mice. In the promotion tests, the chemicals were applied twice a week for 51 weeks after initiation with dimethylbenzanthracene (DMBA). In the tests for complete carcinogenic activities, the chemicals alone were applied for 51 weeks. Benzoyl peroxide was found to be a potent promoter as reported previously. Moreover, possible complete carcinogenic action of this chemical was found in this study. Potential promoting effect was suspected in sodium chlorite. Potassium bromate, ammonium persulphate, hydrogen peroxide and sodium hypochlorite were inactive either as a promoter or a complete carcinogen.
Glandular stomachs of fetal and newborn Wistar rats were transplanted s.c. after treatment in vitro with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) at concentrations of 10, 5 and 1 microgram/ml for 2 h. Eleven adenocarcinomas developed from 118 MNNG-treated transplants, whereas no adenocarcinomas developed from 28 untreated transplants. The incidence of adenocarcinomas in fetal glandular stomach (9/46) was significantly different (p less than 0.01) from that in glandular stomach of newborn rats (2/67). Various types of mesenchymal tumors also developed from untreated (9/28) and MNNG-treated (20/118) transplants.
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An autopsy case of arteriovenous malformation (AVM) of the brain in a 29-year-old housewife was reported. Several important and characteristic findings were obtained by detailed histological examination and micrometric measurement of abnormal vessels composing the nidus of the AVM. Structural imperfectness and immaturity of their vascular wall suggested that the AVM is a histoembryogenic maldevelopment. Prominent dilatation in calibre, hypertrophy of muscular layer, hyalinization, and abnormal increasing of elastic fibers were interpreted as the result of changed cerebral hemodynamics caused by an arteriovenous fistulous communication.
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.
Untreated fetal and newborn glandular stomachs of Wistar rats were transplanted into the subcutis, testis, peritoneal cavity and subcapsular spaces of the kidney or spleen of syngeneic adult rats. The recipients were sacrificed one year after transplantation. Transplantability was very high and the grafted tissues were recovered from more than 80% of the animals at almost all transplantation sites. The transplanted gastric mucosa was well-differentiated morphologically and biochemically. Malignant conversion occurred in 6 of 118 transplants (5%); the tumors were a fibrosarcoma (1), a ganglioneuroblastoma (1), leiomyosarcomas (2) and squamous cell carcinomas (2). No malignant transformation of glandular stomach epithelium was observed.
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Cytosine arabinoside (ara-C), an antiproliferative agent, was given subcutaneously to Sprague-Dawley rats on the 2-4th postnatal day in doses of 12.5 and 25 mg/kg/day. Body weight and viability were found to be dose-dependently inhibited. The appearance of audio-startle response was delayed in the group on the high dose and up to 21 days of age, the ambulatory behavior resembled that seen in geriatric rats. The free-fall righting reflex failed to appear in the treated groups. The open field test revealed that only the treated females were hypoactive. The treated group showed a poor neuro-muscular ability in the rotarod performance and impairment of acquiring conditioned and unconditioned avoidance response in pole climbing. Histopathological and biochemical studies revealed a hypoplasia of the cerebellum. These findings are suggestive of behavioral dysfunction caused by ara-C-induced cerebellar disorders.
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