Regulation by ionizing radiation of CDC2, cyclin A, cyclin B, thymidine kinase, topoisomerase IIalpha, and RAD51 expression in normal human diploid fibroblasts is dependent on p53/p21Waf1

摘要: Induced cell cycle delays were among the first described cellular responses to ionizing radiation (IR). To understand sensitivity and molecular events involved in response low doses of IR examine role p53 its downstream effector p21Waf1, we measured changes expression genes postulated be IR. Expression levels examined normal human diploid fibroblasts irradiated maintained quiescent density-inhibited growth up 24-48 h after exposure X-ray as 0.1-0.3 Gy, which have negligible effects on survival. Among 31 analyzed, observed down-regulation mRNA CDC2, cyclin A, B, thymidine kinase, topoisomerase IIalpha, RAD51. A similar reduction these occurred when cells released from confluence allowed proliferate. This was not function defective up-regulation p21Waf1 either did occur (E6 transfected Li-Fraumeni fibroblasts) or delayed (ataxia telangiectasia irradiation. Down-regulation also absent p21Waf1-null mouse embryo (MEFs) but at a lower level p53-null MEFs, due slight increases by p53-independent pathway. These findings indicate that regulated is p53-dependent involves p21Waf1. Although no G2-M showed delay irradiation, indicating does regulate delay.