Abstract:In the present survey, the historical data for spontaneous tumors observed in our laboratory was compared in relation to the time-related changes between recent (2000)(2001)(2002)(2003)(2004) and past (1990-1999) samples from Fischer 344 rats used in carcinogenicity studies. In the recent samples, there were statistically increased incidences of islet cell adenomas in males and uterine adenocarcinomas in females. On the other hand, there were decreased incidences of pheochromocytomas, prostatic adenomas, pituitary anterior adenomas, large granular lymphocytic (LGL) leukemias and Leydig cell tumors in males and pituitary anterior adenomas in females. Furthermore, there were decreases in the body weights of both sexes at 58 weeks of age in the recent samples, and this may have been related to the decreases in the incidences of pheochromocytomas, Leydig cell tumors, prostatic adenomas and LGL leukemias. Moreover, the decreased incidence of pheochromocytoma in males revealed a positive correlation with a decreased percentage of severe chronic progressive nephropathy (CPN). On the other hand, there were no distinct factors responsible for increased incidences of tumors observed in the recent samples, suggesting a possible genetic drift. In conclusion, the incidences of spontaneous tumors obtained in our laboratory have been changed with time. Smaller body weights in both sexes and reduction in the number of male cases with severe CPN might be related to the reduced incidence of certain types of tumors in recent animals. (J Toxicol Pathol 2008; 21: 53-60)
We investigated a case of spontaneous malignant T-cell lymphoma observed in a 19-week-old male Crl:CD (SD) rat. The rat showed paralysis beginning 1 week before euthanasia. Hematological examination revealed marked lymphocytosis without distinct atypia. Macroscopically, hepatosplenomegaly and partial atrophy of the thoracic spinal cord were observed. Microscopically, neoplastic cells infiltrated into the liver, splenic red pulp, bone marrow and epidural space of the thoracic spinal cord, while no neoplastic cells were observed in the thymus and lymph nodes. Moreover, the spinal cord showed focal degeneration due to compression by marked infiltration of neoplastic cells in the subdural space. The neoplastic cells were generally small-sized round cells that had a round nucleus with/without a single nucleolus and scanty cytoplasm. Immunohistochemically, the neoplastic cells were positive for CD3 and CD8 and negative for CD79α. Judging from these results, the present tumor in this young adult rat was diagnosed as malignant T-cell lymphoma.
Extraskeletal osteosarcoma is a very rare tumor in humans and animals including rats. This paper describes a case of extraskeletal osteosarcoma observed in the glandular stomach of an aged female Fischer 344 rat. Grossly, a whitish solid mass was observed at the greater curvature of the glandular stomach. Histologically, the tumor consisted of both atypical polygonal and pleomorphic spindle-shaped cells, with pleomorphic nuclei, and it contained variable amounts of osteoids and small clumps of mature bone tissue. In addition, mitotic figures were frequently observed. Neither invasion of the muscle layer or vessels in the stomach nor metastasis to distant organs was detected. There were no skeletal tumors in the body. Immunohistochemically, the tumor cells were positive for osteocalcin, osteonectin, vimentin and S-100 protein. Judging from these results, the present tumor was diagnosed as extraskeletal osteosarcoma. This is the first report of spontaneous extraskeletal osteosarcoma arising from the stomach in a rat.
-This study was designed to evaluate changes in auditory brainstem response (ABR) in the course of auditory disturbance in rats induced by Kanamycin (KM). KM was administered subcutaneously to 12 CD (SD) male rats aged 6 weeks for 10 days at a dose of 800 mg/kg. Death was observed in one male on day 8 and 2 males on day 10. It was thought that kidney damage was the cause of death from histopathological findings. ABR was recorded before KM treatment and on days 4, 8, 10 and 11 after KM treatment. The ABR changes after KM treatment in rats were as follows. On day 4, 6 rats showed an increase in amplitude of waves I and/or II and on day 8, among those, 4 rats still showed a high amplitude of waves I and/or II. On day 8, 2 rats showed an elevation of ABR threshold (15-40 dB SPL) and a decrease in amplitude of wave I and increase in amplitude of wave II at the same time. On day 11, 7 rats showed a decrease in amplitude of wave I. In addition, ABR threshold shifts 10-70 dB SPL were observed in those rats. In ABR recording, KM-induced auditory disturbance model rats showed an increase in amplitude of waves I and/or II earlier than an ABR threshold shift. By analyzing temporal alteration of amplitude of the ABR components, we could detect precursory phenomenon of the auditory disturbance at an early phase of treatment. By following the pathway of click-ABR and tone pip-ABR examination, the auditory disturbance of low-frequency to high-frequency range could be analyzed at an early date in detail.
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