caa a22 4500 445853999 CHVBK 20180317145422.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s00204-010-0557-1 doi (NATIONALLICENCE)springer-10.1007/s00204-010-0557-1 Immunohistochemical analyses at the late stage of tumor promotion by oxfendazole in a rat hepatocarcinogenesis model [Elektronische Daten] [Yasuaki Dewa, Jihei Nishimura, Meilan Jin, Masaomi Kawai, Yukie Saegusa, Sayaka Kenmochi, Keisuke Shimamoto, Tomoaki Harada, Makoto Shibutani, Kunitoshi Mitsumori] 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 200mg/kg N-diethylnitrosamine, and 2weeks later they were fed a diet containing 0% (basal diet) or 0.05% OX for 26weeks. 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. Springer-Verlag, 2010 Oxfendazole nationallicence Oxidative stress nationallicence Cell proliferation nationallicence Apoptosis nationallicence CYP1A enzyme induction nationallicence Hepatocarcinogenesis nationallicence Dewa Yasuaki Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, 183-8509, Tokyo, Japan aut Nishimura Jihei Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, 183-8509, Tokyo, Japan aut Jin Meilan Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, 183-8509, Tokyo, Japan aut Kawai Masaomi Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, 183-8509, Tokyo, Japan aut Saegusa Yukie Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, 183-8509, Tokyo, Japan aut Kenmochi Sayaka Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, 183-8509, Tokyo, Japan aut Shimamoto Keisuke Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, 183-8509, Tokyo, Japan aut Harada Tomoaki Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, 183-8509, Tokyo, Japan aut Shibutani Makoto Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, 183-8509, Tokyo, Japan aut Mitsumori Kunitoshi Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, 183-8509, Tokyo, Japan aut Archives of Toxicology Springer-Verlag 85/2(2011-02-01), 155-162 0340-5761 85:2<155 2011 85 204 https://doi.org/10.1007/s00204-010-0557-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-010-0557-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Dewa Yasuaki Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, 183-8509, Tokyo, Japan aut NATIONALLICENCE 700 1- Nishimura Jihei Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, 183-8509, Tokyo, Japan aut NATIONALLICENCE 700 1- Jin Meilan Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, 183-8509, Tokyo, Japan aut NATIONALLICENCE 700 1- Kawai Masaomi Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, 183-8509, Tokyo, Japan aut NATIONALLICENCE 700 1- Saegusa Yukie Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, 183-8509, Tokyo, Japan aut NATIONALLICENCE 700 1- Kenmochi Sayaka Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, 183-8509, Tokyo, Japan aut NATIONALLICENCE 700 1- Shimamoto Keisuke Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, 183-8509, Tokyo, Japan aut NATIONALLICENCE 700 1- Harada Tomoaki Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, 183-8509, Tokyo, Japan aut NATIONALLICENCE 700 1- Shibutani Makoto Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, 183-8509, Tokyo, Japan aut NATIONALLICENCE 700 1- Mitsumori Kunitoshi Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, 183-8509, Tokyo, Japan aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/2(2011-02-01), 155-162 0340-5761 85:2<155 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer