Altered expression of GADD45 genes during the development of chemical-mediated liver hypertrophy and liver tumor promotion in rats
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- Ozawa Shogo
- Department of Pharmacodynamics and Molecular Genetics, School of Pharmacy, Iwate Medical University
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- Gamou Toshie
- Department of Pharmacodynamics and Molecular Genetics, School of Pharmacy, Iwate Medical University
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- Habano Wataru
- Department of Pharmacodynamics and Molecular Genetics, School of Pharmacy, Iwate Medical University
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- Inoue Kaoru
- Division of Pathology, National Institute of Health Sciences
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- Yoshida Midori
- Division of Pathology, National Institute of Health Sciences
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- Nishikawa Akiyoshi
- Division of Pathology, National Institute of Health Sciences
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- Nemoto Kiyomitsu
- Department of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka
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- Degawa Masakuni
- Department of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka
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The purpose of our study was to examine the altered gene expression associated with nongenotoxic chemical-mediated liver hypertrophy and successive liver tumor promotion. Five-week-old male rats were fed a basal diet or a diet containing phenobarbital (PB) or clofibrate (CF) for 3 days, 4 weeks, and 13 weeks. Hepatic expression profiling of cell growth- and stress-related genes, as well as those involved in xenobiotic metabolism, was performed by DNA microarray and/or real time quantitative reverse transcription-polymerase chain reaction. The induction of liver hypertrophy and hepatic cytochrome P450 (CYP) isoforms (CYP2B1/2B2 for PB and CYP4A1 for CF) by PB and CF were clearly observed at all the treatment periods examined. Genes encoding DNA damage-inducible 45 (GADD45) family proteins, in particular GADD45g (GADD45 gamma) were down-regulated by treatment with either PB or CF for 4 and 13 weeks. The chemical-mediated development of liver hypertrophy, induction of hepatic CYPs, and suppression of hepatic GADD45g gene at week 13 disappeared at 4 weeks following cessation of the chemical treatment. Additionally, DNA microarray data indicated that cell cycle-related genes such as cyclins CCNB1 and CCNA2 and cyclin-dependent kinase inhibitor CDKN3 were also down-regulated by treatment with either PB or CF at 13 weeks. Since GADD45 functions as a chemical and radiation stress sensor by interacting with cyclins and cyclin-dependent kinase inhibitors, the decrease in the gene expression of GADD45g mRNA observed in this study, may be associated with nongenotoxic chemical-induced tumor promotion of hepatocarcinogenesis rather than liver hypertrophy.
収録刊行物
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- The Journal of Toxicological Sciences
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The Journal of Toxicological Sciences 36 (5), 613-623, 2011
一般社団法人 日本毒性学会
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詳細情報 詳細情報について
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- CRID
- 1390282679879384192
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- NII論文ID
- 10029481415
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- NII書誌ID
- AN00002808
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- COI
- 1:CAS:528:DC%2BC3MXhsVylsb%2FO
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- ISSN
- 18803989
- 03881350
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- NDL書誌ID
- 11270388
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- PubMed
- 22008536
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 使用不可