Strong carcinogenic stress response induction of preneoplastic cells positive for GST-P in the rat liver: Physiological mechanism for initiation
| Autor: | Kimihiko Satoh |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine medicine.medical_treatment General Biochemistry Genetics and Molecular Biology Rats Sprague-Dawley Acetylcysteine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Hepatectomy Cytotoxic T cell General Pharmacology Toxicology and Pharmaceutics Enzyme inducer Carcinogen biology Chemistry Liver Neoplasms General Medicine Glutathione 2-Acetylaminofluorene Molecular biology Neoplasm Proteins Rats Gene Expression Regulation Neoplastic 030104 developmental biology Glutathione S-transferase Glutathione S-Transferase pi Enzyme Induction 030220 oncology & carcinogenesis Hepatocytes biology.protein Bile Ducts Precancerous Conditions medicine.drug |
| Zdroj: | Life Sciences. 200:42-48 |
| ISSN: | 0024-3205 |
| DOI: | 10.1016/j.lfs.2018.02.041 |
| Popis: | 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. Significance The cytotoxic action of AAF that give rise to the GST-P+ single hepatocytes was suggested to be an injury to the excretory pump(s) and the duct of hepatocytes. A new physiological mechanism was hypothesized for the induction of preneoplastic cell populations in the rat liver instead of a genetic mechanism. |
| Databáze: | OpenAIRE |
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