Time course of cell cycle-related protein expression in diethylnitrosamine-initiated rat liver.
OBJECTIVE
Cell cycle control and the relationship that exists between cellular proliferation, the expression of cell cycle control proteins and cancer have been reported. This study was designed to decipher the timing of cell cycle control protein expression during the initiation of diethylnitrosamine-induced rat hepatocarcinogenesis.


METHODS
Three-week-old female Sprague-Dawley rats were intraperitoneally injected twice in 1 week with diethylnitrosamine; after the second injection, all animals were sacrificed at 1, 2 and 24 h, and 3 and 7 days. The expression of cell cycle-related proteins such as CDK2 and 4, cyclin proteins (D1, E and cdc2), proliferating cell nuclear antigen, tumor suppressor proteins (p53 and Rb), CDK inhibitory proteins (p21waf1 and p27Kip1), and apoptosis-inhibiting protein (bcl-2) following diethylnitrosamine treatment was examined.


RESULTS
The peak induction time of each cell cycle-related protein during DEN-induced cellular proliferation was diverse, and expressions of CDK2, CDK4, cdc2, p53, bcl-2, p21Waf1 and p27Kip1 appear to be of the greatest interest.


CONCLUSIONS
Data generated from this study may provide information about cell cycle-related protein expression in the initiation stage of hepatocarcinogenic signaling pathways stimulated by a genotoxic agent such as diethylnitrosamine.
Laboratory of Radiation Effect, Korea Cancer Center Hospital, Seoul.
Y S
YS
Lee
W H
WH
Kim
E S
ES
Yu
M R
MR
Kim
M J
MJ
Lee
J J
JJ
Jang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004052:Diethylnitrosamine / Q000633:toxicity*; D005260:Female; D016147:Genes, Tumor Suppressor; D020287:In Situ Nick-End Labeling; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D018797:Cell Cycle Proteins; D016213:Cyclins; D018809:Proliferating Cell Nuclear Antigen; D004052:Diethylnitrosamine; D018844:Cyclin-Dependent Kinases