Time course of cell cycle-related protein expression in diethylnitrosamine-initiated rat liver

Background/Aims: 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 (p21(Waf1) and p27(Kip1)), 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, p21(Waf1), and p27(Kip1) 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.