ABSTRACT
Liposarcoma is a rare neoplasm in rats and is characterized by the presence of lipoblasts containing multiple cytoplasmic vacuoles. We encountered a rare type of liposarcoma in a male SD (Crj:CD(SD)IGS) rat during a long-term study to gather background data. At necropsy at 105 weeks of age, there was a large amount of fatty tissue covering the mesentery, pancreas, and retroperitoneum; a white nodule in the right kidney; and paleness of the liver. Microscopically, the tumor had a well-differentiated component and dedifferentiated high-grade component. Immunohistochemical and electron microscopic examinations revealed that the pleomorphic tumor cells retained the characteristics of lipoblasts. Distant or disseminated metastasis was also confirmed in various organs. A liposarcoma with these histological features is extremely rare in rats, and this is the first report of a highly metastatic dedifferentiated type of liposarcoma originating from the abdominal fat tissue in a rat.
ABSTRACT
The present study was performed to characterize immunohistochemically the expression levels of molecules related to not only xenobiotic and antioxidant functions but also cell proliferation and apoptosis in neoplastic lesions induced by the benzimidazole anthelmintic, oxfendazole (OX), at the late stage of its tumor promotion in a rat hepatocarcinogenesis model. Male F344 rats were initiated with an intraperitoneal injection of 200 mg/kg N-diethylnitrosamine, and 2 weeks later they were fed a diet containing 0% (basal diet) or 0.05% OX for 26 weeks. All animals were subjected to a two-thirds partial hepatectomy at week 3 and killed at week 28. Histopathologically, OX increased the incidence and multiplicity of altered foci (4.0- and 3.6-fold, respectively) and hepatocellular adenomas (HCAs) (3.0- and 5.5-fold, respectively). OX treatment induced 5.2- and 5.6-fold increases in the number of proliferating cell nuclear antigen (PCNA)-positive cells and single-stranded DNA (ssDNA)-positive cells in HCAs compared with the surrounding tissue, respectively. Staining for the cell cycle regulators P21 and C/EBPα and the AhR-regulated CYP1A1 molecules decreased but increased reactivity of the Nrf2-regulated, detoxifing/antioxidant molecules aldo-keto reductase 7 (AKR7) and glutathione peroxidase 2 (GPX2) were also seen in HCAs compared with the surrounding hepatocytes. These results suggest that dysregulation of cell proliferation and apoptosis and escape from oxidative stress elicited by OX treatment play an important role in OX-induced hepatocarcinogenesis in rats.
