期刊
LIFE SCIENCES
卷 200, 期 -, 页码 42-48出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2018.02.041
关键词
Initiation; Hepatocarcinogenesis; Glutathione S-transferase; 2-acetylaminofluorene; Vibratome
资金
- Nippon Boehringer-Ingelheim Company (Osaka, Japan)
- Ministry of Education, Culture, Sports, Science and Technology, Japan [61210002, 60570104, 05807009, 07457579]
- Grants-in-Aid for Scientific Research [07457579, 05807009, 60570104] Funding Source: KAKEN
Aims: To identify experimental conditions that induce preneoplastic cells positive for glutathione S-transferase P-form (GST-P) in the rat liver by new approaches, and analysis of the mechanism of cancer initiation based on the findings. Main methods: The experimental protocols employed to induce GST-P+ preneoplastic cells in rat liver were as follows. Protocol 1: adult rats were fed basal diet containing 2-acetylaminofluorene (AAF, 0.02% by wt) and high concentrations of N-acetyl-L-cysteine (0.5%) over 10 weeks. Protocol 2: rats were subjected to partial hepatectomy (2/3PH), followed by an AAF (0.04%) diet for two more weeks. Vibratome-prepared liver sections were then immunostained for GST-P. Key findings: GST-P was inducible in the rat liver in response to the strong carcinogenic stress by AAF in the two experimental protocols. When examined immunocytochemically with vibratome sections, the biliary tracts of hepatocytes, GST-P+ single hepatocytes and foci were heavily positive for the marker enzyme in addition to ordinary cytosolic staining of preneoplastic cell populations. The biliary tracts of hepatocytes were severely injured, and the excretory portions of GST-P+ single hepatocytes were significantly injured.
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