Changes in expression of cell cycle regulators after G1 progression upon repetitive thioacetamide treatment in rat liver.
- Author:
Sook Hee HONG
1
;
Gie Deug LEE
;
Jun Young CHUNG
;
Kyung Sook CHO
;
Seok Hee PARK
;
In Hoo KIM
;
Jin Sook JEONG
Author Information
1. Department of Pathology, Dong-A University College of Medicine, Busan, Korea. jsjung1@daunet.donga.ac.kr
- Publication Type:Original Article
- Keywords:
cyclin G1;
G2 arrest;
p53;
rat liver;
thioacetamide
- MeSH:
Animals;
Bromodeoxyuridine/metabolism;
CDC2 Protein Kinase/drug effects/metabolism;
*CDC2-CDC28 Kinases;
Cell Cycle/drug effects/*physiology;
Cell Cycle Proteins/drug effects/metabolism;
Cyclin-Dependent Kinases/antagonists & inhibitors/drug effects/metabolism;
Cyclins/drug effects/metabolism;
Dose-Response Relationship, Drug;
G1 Phase/drug effects/*physiology;
Liver/*drug effects/pathology;
Male;
Nuclear Proteins/drug effects/metabolism;
Proliferating Cell Nuclear Antigen/metabolism;
Protein p53/metabolism;
Protein-Serine-Threonine Kinases/antagonists & inhibitors/drug effects/metabolism;
Rats;
Rats, Sprague-Dawley;
Thioacetamide/administration & dosage/*pharmacology;
Tumor Suppressor Proteins/drug effects/metabolism
- From:Experimental & Molecular Medicine
2002;34(5):361-366
- CountryRepublic of Korea
- Language:English
-
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).
