Expression of p21waf1/cip1 Is Induced in the Rat Liver by Feeding of 2-Acetylaminofluorene.
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概要
- 論文の詳細を見る
The cyclin-dependent kinase inhibitor p21wafl/cipl plays major role in regulation of the cell cycle arrest following DNA damage in a p53-dependent and -independent manner. To elucidate the roles of p21wafl/cipl in selective growth of preneoplastic lesions during chemical hepatocarcinogenesis, p21wafl/cipl expression was examined in the livers of rats fed a 0.02% 2-acetylaminofluorene (2-AAF)-containing diet for 4 weeks or subjected to the protocol of Solt and Farber consisting of a single dose of diethylnitrosamine (DEN) followed 2 weeks later by 2-AAF feeding with two-thirds hepatectomy. By feeding of 2-AAF having a strong mitoinhibitory effect, p21wafl/cipl expression was significantly induced in rat hepatocytes. The proliferating cell nuclear antigen (PCNA) labeling index of hepatocytes was consistently and significantly decreased by 2-AAF feeding. Immunohistochemically, both p21wafl/cipl and p53 were detected in the livers of 2-AAF-fed rats more intensely than in those of control rats. In the livers of rats subjected to the protocol of Solt and Farber, most enzyme-altered foci (EAF) were immunohistochemically negative for p21wafl/cipl, while hepatocytes surrounding the foci were positive. These results clearly show that 2-AAF acts on hepatocytes as a mitoinhibitor by inducing p21wafl/cipl expression, presumably in a p53-dependent manner. Furthermore, the marked difference in p21wafl/cipl expression between non-neoplastic and preneoplastic hepatocytes led to selective growth of preneoplastic lesions during 2-AFF feeding using the protocol of Solt and Farber.
- 日本毒性病理学会の論文
著者
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WATANABE Tomoyuki
Environ. Health Science Lab., Sumitomo Chem. Co., Ltd.
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Ozaki Masakazu
Environmental Health Science Laboratory Sumitomo Chemical Co. Ltd.
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Kawasaki Hajime
Environmental Health Science Laboratory Sumitomo Chemical Co. Ltd.
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Kojima Takashi
Department Of Applied Chemistry And Biotechnology Chiba University
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Watanabe Tomoyuki
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd.
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Sawada Norimasa
2nd Department of Pathology, Sapporo Medical University School of Medicine
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