Biomedical subjects

A Todate

Publications and source records attributed to A Todate.

27 records · Page 2Linked to original sources

PubMed1990

Spontaneous uterine adenocarcinomas in aged rats and their relation to endocrine imbalance.

In addition to spontaneous uterine endometrial adenocarcinomas at a high incidence (35.1%), development of endometrial hyperplasia/adenoma was also frequently detected in rats of the Donryu strain. The total yield of all observed proliferative endometrial lesions was very high (60.6%). The tumors arose commonly in the uterine horn of aged rats. Histologically, most demonstrated glandular structures, consisting of cuboidal or columnar cells with weak eosinophilic or basophilic cytoplasm and large nuclei. In about half of the animals with adenocarcinomas, metastasis to remote organs such as the lung was observed. Histological examination of the ovary and vaginal epithelium revealed ovarian cysts, atrophy of the ovary and cornification of the vaginal epithelium more frequently in rats with endometrial carcinomas than in animals without tumors. These findings indicate that adenocarcinoma development in Donryu rats is associated with endocrine imbalance [increased serum estrogen: progesterone (E2:P)ratios]. By comparative investigation of strain differences, it was confirmed that irregular estrous cycles began earlier with higher incidence in Donryu rats than in F344 rats, a low-incidence strain. Histological findings of the ovary and vaginal epithelium also suggested relatively increased estrogen levels in Donryu rats compared to F344 rats. Estimated plasma values of gonad steroids showed that the E2:P ratio in Donryu rats at 12 months of age was about five times that in F344 rats. These results therefore indicate that hormone imbalance, particularly an increased E2:P ratio, may play an important role in the spontaneous occurrence of endometrial adenocarcinoma in Donryu rats.

Adenocarcinoma↗

PubMed1990

Lack of toxicity/carcinogenicity of monosodium succinate in F344 rats.

The toxicity/carcinogenicity of monosodium succinate, a food additive, was examined in F344 rats. The oral LD50 was greater than 8 g/kg body weight. In a 13-wk subchronic oral toxicity study, the only toxicological finding was suppression of body-weight gain in groups given greater than or equal to 2.5% monosodium succinate in the drinking-water. Histological examination revealed no toxic lesions specifically caused by the compound in any organs of any of the treated rats. The maximum tolerated dose was determined to be 2-2.5% on the basis of body-weight depression. In a long-term (2-yr) toxicity/carcinogenicity study, monosodium succinate was given ad lib. in drinking-water (distilled water) at levels of 0, 1 or 2% to groups of 50 male and 50 female rats. No toxic lesion specifically caused by long-term administration of monosodium succinate was detected. No dose-related increase was found in the incidences of tumours in any organ or tissue except for C-cell tumours of the thyroid gland of females. The incidence of these tumours in females given the 2% dose was higher than that in controls but not significantly so, and a positive trend for this tumour was noted in females. C-Cell tumour is one of the most commonly observed spontaneous tumours in ageing female rats of this strain and occurs at a variable incidence. There was no difference between the female control and treated groups in the incidence of preneoplastic change of the thyroid gland. Furthermore, the incidence of C-cell tumours in the female control group was lower than that in our historical controls. It is concluded that the increase in C-cell tumours in the female high-dose group and the detection of a positive trend for this tumour in females were probably a function of experimental variability and were not related to treatment. The results indicate that monosodium succinate had neither toxic nor carcinogenic activity in F344 rats when it was given continuously at levels of 1 or 2% in the drinking-water for 2 yr.

Animals↗

PubMed1990

High yields of granulosa cell tumors/luteomas in F344 rat ovaries after transplacental administration of N-nitrosobis(2-oxopropyl)amine.

Ovarian tumors were induced at very high incidence in the offspring of F344 rats receiving 3 subcutaneous injections of 10 mg/kg of N-nitrosobis(2-oxopropyl)amine on the 14th, 18th and 20 days of gestation. Histologically, all ovarian tumors were of the granulosa cell tumor and/or luteoma type. Many of them consisted of large, polygonal cells with abundant eosinophilic or vacuolated cytoplasm, arranged in sheets or in a pseudo-palisaded pattern separated by thin fibrovascular stroma, and they exhibited typical luteoma morphological character. The high yields, and the similarities in morphology as well as putative hormonal influence suggest that this experimental system may serve as a good animal model for granulosa cell tumor and/or luteoma development in women.

Animals↗

PubMed1990

[Subchronic oral toxicity study of tannic acid in F344 rats].

A 13-week subchronic oral toxicity study of tannic acid (TA) was carried out in F344 rats at dose levels of 0, 0.025, 0.05, 0.1, 0.2 and 0.4% in the drinking water, to determine appropriate dose levels for a subsequent 2-year carcinogenicity study. The rats were randomly allocated to 6 groups, each consisting of 12 males and 12 females. No animals died during the administration period. There were no significant difference in body weight gain, food consumption and organ weights between the treated and control groups, although a slight decrease in water intake was seen in the 0.4% TA treated group. No specific changes were observed in any parameters in the hematological and biochemical investigations. Histopathological examination, revealed toxic changes in the TA treated male groups, in the form of necrosis in the liver, but toxicologically it was of minor importance. From these results, it was concluded that the provable maximum tolerable dose of TA in the drinking water would be more than 0.4%. In consideration of the avoidance of drinking water, the maximum tolerable dose of tannic acid was determined to be 0.5%, when given in the drinking water.

Administration, Oral↗

PubMed1989

Teratoma of the pituitary gland in a young male rat.

A pituitary teratoma was found in a 5-week-old (37-day-old) male Donryu rat. The tumour (10 x 11 x 9 mm) was round in shape and white in colour. The cut surface was solid without haemorrhagic or cystic change. Histologically, it was composed of various kinds of tissue components including mature and immature elements derived from the three embryonic germ layers, i.e., nervous tissue, cartilage, bone, squamous epithelial element, glandular element lined by one or more layers of ciliated columnar or cuboidal epithelial cells, striated muscle tissue, adipose tissue and connective tissue. Neuroepithelial rosettes and immature or embryonal epithelium as well as immature cartilage were intermingled with mature somatic tissues.

Animals↗

PubMed1989

Dose-response carcinogenicity in rats on low-dose levels of N-ethyl-N-nitrosourethane.

A dose-response study on the carcinogenicity of N-ethyl-N-nitrosourethane (ENUR) was undertaken to examine its effect at low doses. Six-week-old female F344 rats were divided into 5 groups, each consisting of 40 animals. ENUR was dissolved in distilled water at dose levels of 0 (control), 0.15, 0.6, 2.5 and 10 ppm, and rats were given these solutions ad libitum for 2 years. Significant increase of the total tumor incidences and shortening of the mean survival times were observed in groups given 2.5 and 10 ppm ENUR. In groups given 0.6 ppm or more ENUR, digestive tract tumors were induced dose-dependently. They were restricted to the upper digestive tract from the oral cavity to the forestomach, and were histologically squamous cell papillomas or carcinomas. Dose-related differences in the location and incidence of these tumors were found. The virtually safe doses (VSDs) calculated by using the Weibull, Logit and Probit models were 0.365 x 10(-2), 0.110 x 10(-1) and 0.779 x 10(-1) ppm, respectively. The VSDs estimated in the present study are discussed in comparison with those of other carcinogens.

Administration, Oral↗

PubMed1989

[Subchronic oral toxicity study of calcium lactate in F344 rats].

A subchronic toxicity study of calcium lactate was carried out in male and female F344 rats to estimate the maximum tolerated dose for a subsequent long-term toxicity/carcinogenicity study. Experiment I: Rats were divided into 6 groups, each consisting of 5 males and 5 females. Calcium lactate was dissolved in water at concentrations of 5, 2.5, 1.25, 0.6, 0.3 and 0%, each animal group was given one of these solutions as the drinking water for 13 wk. In all groups, basic diet (CRF-1) was given ad libitum. No fatalities occurred. In all treated groups, including the 5% group, a less than 10% depression of body-weight gain as compared with the control group was observed. Some parameters in the hematological and biochemical data demonstrated change in the treated groups. On histological examination, however, no severe toxicological findings were found in any of the treated groups. Experiment II: Rats were fed synthetic diet B, containing 30, 20, 10, 5 or 0% calcium lactate. In the highest dose group, body weight-gain was strongly reduced as compared with the control group. Histological examination revealed nephrocalcinosis in all groups, including the control group, and adverse dose-effect relation was observed with regard to degree of its development. Females exhibited this lesion to a greater extent than males. Experiment III: Rats were given CRF-1 or synthetic diet B for 8 wk. Nephrocalcinosis was found only in the group given synthetic diet. It was ascertained that the nephrocalcinosis observed in Exp. II and III was dependent on the low Ca/P ratio (Ca/P: less than 1) of the synthetic diet B.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Carcinogenicity and organ specificity of N-trimethylsilylmethyl-N-nitrosourea (TMS-MNU), N-neopentyl-N-nitrosourea (neoPNU), and N-methyl-N-nitrosourea (MNU) in rats.

The carcinogenicity and organ specificity of TMS-MNU and neoPNU, a carbon-analogue of TMS-MNU, in rats were investigated and compared with those of MNU. Compounds were dissolved in olive oil and rats in the experimental groups received 20 weekly intragastric intubations of 10 mg/kg of MNU or equimolar amounts of TMS-MNU or neoPNU in the same manner. The experiment was terminated when the survivors were sacrificed at the 52nd week after the final administration. In the TMS-MNU and MNU groups, tumors of the forestomach were induced and the incidence was 100% in the groups of both sexes. In addition, tumors of the glandular stomach, nervous system, kidney, and lung were also observed in these groups. Neurogenic tumors were found more frequently in the MNU group than in the TMS-MNU group. The incidence of lung tumors, however, was higher in the TMS-MNU group than in the MNU group. On the other hand, in the control and neoPNU groups, no tumor was found in these organs except the lung, and all tumors observed in these two groups were histologically similar to spontaneous ones in this strain of rats. These results indicate that the carcinogenicity of N-alkyl-N-nitrosoureas is dependent on the chemical structure of their alkyl chain. The result of the present study coincides with the previous result that the species of TMS-MNU in the alkylating step is the same as that of MNU, but different from neoPNU. The difference in the organ specificity between TMS-MNU and MNU demonstrates that the organ specificity is dominantly dependent on the distribution of the chemicals, since TMS-MNU may possibly be distributed differently from MNU because of its different partition property.

Animals↗

PubMedDate not supplied

Dual effects of prolonged ACTH stimulation on 4-hydroxyaminoquinoline 1-oxide-induced adrenocortical lesions in rats.

The effects of a long-acting synthetic ACTH on 4-hydroxyaminoquinoline 1-oxide (4HAQO)-induced adrenocortical lesions were investigated in female rats. A total of 140 6-week-old rats were divided into 4 equal groups, given a single s.c. injection of 7 mg/kg 4HAQO or vehicle, followed by repeated sc administration of the synthetic ACTH or no further treatment. Subgroups of 10 rats in each group were sequentially sacrificed at weeks 20, 30, and 40. Adenomas and adenomatous nodules developed in the adrenal cortex of animals receiving 4HAQO and the chronic ACTH stimulation. Both lesions were located in the deeper zones of the adrenal cortex adjacent to the medulla and were composed of large-sized, clear-type cells. From week 20, middle zone, cortical cystic degeneration, which mimics the age-associated degenerative change named adrenal peliosis, was frequently observed in the adrenal glands of animals treated with 4HAQO alone. Its development was inhibited by ACTH. In the control animals, peliotic changes occurred at low incidence and only at the termination of experiment. These results indicate that long-term stimulation of ACTH promotes the development of adrenocortical tumors but suppresses the occurrence of adrenal peliosis in rats treated with 4HAQO.

4-Hydroxyaminoquinoline-1-oxide↗