A mammary fibroadenoma with terminal end buds-like structures in a 7-week-old male SD rat.

We report a case of mammary fibroadenoma in a 7-week-old male SD rat. This case showed rapid growth within one week from the time when the nodule was detected. Histologically, the nodule was a well-circumscribed subcutaneous mass. The tumor consisted of an epithelial component with island-like proliferation (cribriform to tubular patterns) and an abundant mesenchymal component. Alpha-SMA-positive cells were arranged at the periphery of the epithelial component and showed cribriform and tubular patterns. Discontinuous basement membranes and high cell proliferative activities were observed in the cribriform area. These features resembled those of normal terminal end buds (TEBs). Since the mesenchymal component had abundant fine fibers and a mucinous matrix, its stroma was regarded as neoplastic growth of fibroblasts; thus, this tumor was diagnosed as a fibroadenoma. This case is an extremely rare fibroadenoma in that it occurred in a young male SD rat and was composed of an epithelial component showing multifocal proliferation of TEB-like structures and a mucinous mesenchymal component consisting of fibroblasts with fine collagen fibers.

Changes in 5-Fluorouracil-induced external granular cell damage during the time-course of the developing cerebellum of infant rats.

5-Fluorouracil (5-FU) is widely used as a chemotherapeutic agent that blocks DNA synthesis and replication by inhibiting thymidylate synthetase. This study aimed to elucidate 5-FU-induced changes in the external granular cells (EGCs) in the cerebellum of infant rats and the possible underlying mechanism. Six-day-old infant rats were injected subcutaneously with 40 mg/kg of 5-FU, and their cerebellums were examined at 6, 9, 12, and 24 h after treatment (HAT), and 2, 4, and 10 d after treatment (DAT). The width of the external granular layer (EGL) decreased from 24 HAT to 4 DAT in the 5-FU group compared to that in the control group. However, the width in the 5-FU group was comparable to that of the control group at 10 DAT. The number of apoptotic cells, cleaved caspase 3-labeling index (LI%), p21cip1-LI%, and expression levels of p53, p21cip1, and Fas mRNAs increased at 24 HAT. However, no changes were detected in the expression levels of Puma and Bax mRNAs at any time point. BrdU-LI% increased at 6 and 12 HAT but decreased at 24 HAT. The phospho-histone H3-LI% decreased from 6 HAT to 2 DAT. The width of the molecular layer decreased compared to that of the control group at 10 DAT. No differences were observed in Purkinje cell development. These results indicate that 5-FU inhibited cell proliferation by inducing apoptosis of EGCs via activation of Fas and caspase-3 without the involvement of the mitochondrial pathway and induced p53-dependent G1-S and G2-M phase arrest.

Malignant pinealoma observed in the deep cerebral parenchyma of a male Wistar rat.

This report describes a case of spontaneous malignant pinealoma in a 90-week-old male Wistar rat. The tumor mass occurred in the deep cerebral parenchyma and no intact pineal gland was observed in the area between the posterior-dorsal median line of the cerebrum and the cerebellum. The tumor was characterized by a large nodular proliferation occupying the central area of the brain, extending from the dorsal surface to the base of the brain, corresponding to the thalamus. The tumor cells had round to irregular oblong nuclei approximately 5-17 µm in diameter and showed faintly or moderately eosinophilic cytoplasm and indistinct cell boundaries. Immunohistochemically, the tumor cells were positive for synaptophysin and partially positive for neuron-specific enolase (NSE). The tumor showed malignant features including cellular pleomorphism, high mitotic index, necrotic foci, and invasive and extensive growth and was, therefore, diagnosed as an extremely rare malignant pinealoma in the deep cerebral parenchyma.

Time-course changes in 5-fluorouracil-induced neural progenitor cell damages in the developing rat brain.

5-Fluorouracil (5-Fu) is a DNA-damaging agent and teratogenic in rodents. This study aimed to investigate its influence on neural progenitor cells (NPCs) in the developing fetal rat brain. Dams were intraperitoneally injected with 5-Fu (50 mg/kg b.w.) on gestation day 13 and its effects on fetal NPCs were observed from 3 to 72 hours after treatment (HAT), via periodic examination at six intervals. In NPCs of the fetal brain, the p53-labeling index (LI%) was markedly elevated at 3 HAT. Pyknosis and cleaved caspase-3-LI% also increased at 3 HAT, reaching peak values at 9 and 12 HAT. These parallel changes suggested the induction of apoptosis through a p53-mediated pathway. Pyknotic NPCs were distributed across the ventricular zone (VZ) of the telencephalic wall until 12 HAT, and became localized in the medial and dorsal layers at 12 and 48 HAT. Significant decreases in the numbers of mitotic NPCs and BrdU-LI% were noted from 3 HAT and 24 HAT, respectively. BrdU-positive NPCs were located in the ventral and middle layer at 24 and 48 HAT. p21-positive cells were detected at 12 and 24 HAT. The present results demonstrated that p53-mediated apoptosis was induced in all phases of the cell cycle of the NPCs in the early stage after 5-FU treatment. Furthermore, apoptosis of NPCs and suppression of cell proliferative activity are the events that take place in parallel leading to prominent reduction in the width of the telencephalic wall.

Natural occurrence of neoplastic lesions in young sprague-dawley rats.

It is important for the assessment of toxicological effects of chemicals to know what kinds of neoplasms naturally occur in the early life of experimental animals. In the present study, we demonstrated spontaneous neoplasms in Sprague-Dawley rats used in 4-, 13- and 26-week toxicity studies conducted at Bozo Research Center in the last decade. The tumors, which were first observed in 19-week-old animals, included anterior adenoma of the pituitary, follicular cell adenocarcinoma and C cell adenoma of the thyroids, nephroblastoma of the kidneys, basal cell tumor of the skin and malignant lymphoma. Thereafter, hemangiosarcoma of the tongue, adenocarcinoma of the submandibular glands, histiocytic sarcoma of the spleen, oligodendroglioma of the brain and adenocarcinoma and fibroadenoma of the mammary glands were detected in 32-week-old animals. The incidences of mammary adenocarcinoma and pituitary anterior adenoma were higher than those of other tumors. The present results showed that the same tumors as reported in aged rats could also develop in younger rats.

A Case of Olfactory Neuroblastoma Induced in A Rat by N-Nitrosobis(2-hydroxypropyl)amine.

N-nitrosobis(2-hydroxypropyl)amine (BHP) is a well-known carcinogen and induces tumors in various tissues. In the present paper, a case of olfactory neuroblastoma (ONB) induced in a rat by BHP is described. The tumor was observed in one out of 25 male rats that received 2000 ppm of BHP in drinking water from 6 to 18 weeks of age and were sacrificed at 26 weeks of age. Histologically, the tumor arose in the posterior nasal cavity and consisted of small round cells and elongate cells with scant basophilic cytoplasm. The neoplastic cells proliferated with compartmentalization into the lobules by fibrovascular septa. True rosettes, pseudorosettes and an intercellular fibrillar matrix were occasionally observed. Immunohistochemically, the tumor cells were positive for NF120/200 and ß III-tubulin. These results indicate that the present tumor is the first case of ONB induced in a rat by BHP treatment.