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The present study was performed to determine whether testicular toxicity can be detected of the administration of adriamycin (ADR), an anticancer drug, for 2 weeks. ADR was intravenously administered to Slc:SD male rats at 1 mg/kg once a week for 4 or 2 weeks, and 2 mg/kg once a week for 2 weeks. Suppression of body weight gain was observed in the 1 mg/kg/week (4 w) and 2 mg/kg/week (2 w) groups. The testes weights in these groups were also lower than those of the control group. On histological examination, a decrease in spermatogonia was observed in the 1 mg/kg/week (4 w) and 2 mg/kg/week (2 w) groups. No abnormalities were detected in the control and 1 mg/kg/week (2 w) groups. Stage analysis of seminiferous tubules was performed for control and 1 mg/kg/week (2 w) groups. In the 1 mg/kg/week (2 w) group, the numbers of spermatogonia in stages II-III, V and XII-XIII were significantly decreased. The numbers of preleptotene spermatocytes in stage VII and zygotene spermatocytes in XII-XIII were also significantly reduced in the same group. These findings suggest that the testicular toxicity of ADR can be detected after 2 weeks administration at a sufficient high dosage, if simplified morphometrical analysis is used.

Scanning electron microscopic observation of the organ of Corti was conducted in kanamycin (KM)-treated beagle dogs, which were subjected to time lapse recording of auditory brainstem response (ABR). KM was administered subcutaneously 5 times per week to 4 beagle dogs at doses of 250 and 500mg/kg for 3-6weeks (a total dose of 4,750 to 7,000mg/kg). The animals were subjected to pathological examination when definite changes in ABR appeared.Severity of morphological changes were closely related with the degree of the ABR change and histopathological renal lesion.In the animals with slightly decreased amplitude of wave I of ABR also exhibited only a slight renal lesion. The organ of Corti, however, showed essentially a normal structure in these animals.In the animal manifesting moderate ABR change, renal lesion was moderate and the change of the hair cell in the organ of Corti was slight.The animal with such severe auditory disturbance as flattened ABR waveform showed a severe renal lesion and almost complete damages of the hair cells in the organ of Corti.In the present observation, the characteristics of KM-induced lesion in the organ of Corti in dogs are essentially the same with in other species. In addition, the examination of hearing ability could be done as an item during the course of routine long-term repeated dose study using dogs. (J Toxicol Pathol 7: 8186, 1994)