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• W2018994025 abstract "Peroxisome proliferators (PPs), non‐genotoxic rodent carcinogens, cause the induction of the peroxisomal fatty acid β‐oxidation system, including bifunctional enzyme (BE) and 3‐ketoacyl‐CoA thiolase (TH), in the liver. GST M1 gene is polymorphic in Sprague–Dawley rats, NC‐ and KS‐type. The KS‐type rats showed enhanced susceptibility to ethyl‐α‐chlorophenoxyisobutyrate (clofibrate, CF), one of the PPs. The degree of BE induction was higher in the KS‐type and preneoplastic foci developed after 6–8 weeks of treatment, whereas no foci developed in the NC‐type. In the preset study, factors involved in different BE inducibility were investigated. There were no differences in hepatic peroxisome proliferator‐activated receptor (PPAR) α levels between them. Among various coactivators for PPARα, only steroid receptor coactivator (SRC)‐3 level was higher in the KS‐type. To investigate the association between PPARα and SRC‐3 or other proteins, nuclear extracts from CF‐treated livers were applied to a PPARα column. In the KS‐type, 110, 72, and 42 kDa proteins were bound and these were identified as SRC‐3, BE, and TH, respectively. EMSA supported the binding of these proteins to PPARα associated to the BE enhancer in CF‐treated KS‐type, but not in the NC‐type. Histone H3 acetylation was increased 11‐fold in the KS‐type by CF treatment but not in the NC‐type. As BE and TH are responsible for acetyl‐CoA production and SRC‐3 possesses a histone acetyltransferase activity, these results suggest that enhanced BE induction in the KS‐type livers is due to acetylation‐mediated transcriptional activation and epigenetic mechanisms might be involved in CF‐induced rat hepatocarcinogenesis. ( Cancer Sci 2010; 101: 876–875)" @default.
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• W2018994025 date "2009-12-08" @default.
• W2018994025 modified "2023-10-17" @default.
• W2018994025 title "Histone acetylation and steroid receptor coactivator expression during clofibrate‐induced rat hepatocarcinogenesis" @default.
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• W2018994025 doi "https://doi.org/10.1111/j.1349-7006.2009.01460.x" @default.
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