Exp Mol Med.  2002 Nov;34(5):361-366.

Changes in expression of cell cycle regulators after G1 progression upon repetitive thioacetamide treatment in rat liver

• Hong SH
• Lee GD
• Chung JY
• Cho KS
• Park SH
• Kim IH
• Jeong JS

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).

Keyword

cyclin G1; G2 arrest; p53; rat liver; thioacetamide

MeSH Terms

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