title: Changes in expression of cell cycle regulators after G1 progression upon repetitive thioacetamide treatment in rat liver.
abstract: Repetitive low dose thioacetamide (TA) treatment of hepatocytes was found to induce cells in G2 arrest. In the present study, an attempt was made to investigate alterations in expression of cell cycle regulators after G1 progression in the same repetitive low dose TA treated hepatocytes system and to define the determinators involved in G2 arrest. TA was daily administered intraperitoneally, with a dose of 50 mg/kg for 7 days. Expression levels of cyclin E and CDK2 were similar, increased at day 1 and reached a peak at day 2. And they recycled from day 3 reaching a second peak at day 5. Expression level of cyclin A was similar to p27(Kip1) and p57(Kip2) but not to CDK2 and increased to a peak level at day 2. Expression levels of cyclin B1 and cdc2 were similar although the cyclin B1 level was generally low, decreased from day 1 to basal levels at day 3 and persisted at a low level till day 7. The expression level of cyclin G1 was similar to p53 that peaked at day 3 and again at day 6 elevated over basal level. BrdU-labeled hepatocytic nuclei increased from 12 h, reached a peak at day 2, then decreased, and were not detectable from day 6. The number of PCNA-labeled nuclei increased immediately, peaked at day 2, and maintained till day 7. These results suggest that G2 arrest induced by repeated TA treatment might be p53-dependent, via activation of cyclin G1, rather than inhibition of cyclin B1- cdc2 complex, and inhibitors holding S phase progression might be p27(Kip1) and p57(Kip2).
authors.affiliation: Department of Pathology, Dong-A University College of Medicine, Busan 602-714, Korea.
authors.forename: Sook Hee
authors.initials: SH
authors.lastname: Hong
authors.forename: Gie Deug
authors.initials: GD
authors.lastname: Lee
authors.forename: Jun Young
authors.initials: JY
authors.lastname: Chung
authors.forename: Kyung Sook
authors.initials: KS
authors.lastname: Cho
authors.forename: Seok Hee
authors.initials: SH
authors.lastname: Park
authors.forename: In-Hoo
authors.initials: IH
authors.lastname: Kim
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Jeong
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D016203:CDC2 Protein Kinase / Q000187:drug effects / Q000378:metabolism; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000187:drug effects / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2; D050760:Cyclin-Dependent Kinase Inhibitor p27; D050761:Cyclin-Dependent Kinase Inhibitor p57; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D016213:Cyclins / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016193:G1 Phase / Q000187:drug effects / Q000502:physiology*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009687:Nuclear Proteins / Q000187:drug effects / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013853:Thioacetamide / Q000008:administration & dosage / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000187:drug effects / Q000378:metabolism
chemical_list: C493962:Cdkn1b protein, rat; D018797:Cell Cycle Proteins; D050761:Cyclin-Dependent Kinase Inhibitor p57; D016213:Cyclins; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D013853:Thioacetamide; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; C495892:Cdk2 protein, rat; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D001973:Bromodeoxyuridine