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ヒトの正常細胞における放射線によるp53蛋白質への情報伝達：ゴーシュJ.C.、鈴木啓司、児玉靖司、渡邉正己(長崎大・薬・放射線生命)

p53 protein accumulation through signal transduction pathway in normal human cells following X-irradiation: J.C.GHOSH, Keiji SUZUKI, Seiji KODAMA and Masami WATANABE (Lab. Radiat. & Life Sci., Schl. Pharm. Sci., Nagasaki University)

p53 is a nuclear phosphoprotein whose function is required for transactivation of a set of genes involved in cell cycle regulation, DNA replication and apoptosis of cells exposed to ionizing radiation. The mechanism of p53 protein accumulation is still remain elusive. Therefore, we investigated signal transduction pathway which led to p53 protein accumulation in normal human embryonic cells following X-irradiation. The accumulation kinetics of p53 protein was two-phasic after 2 or 4 Gy of X-rays, while one peak was observed at 2 hrs after 6 Gy of X-rays. The first accumulation of p53 reached maximum at 2 hours and second accumulation reached maximum between 8 to 12 hrs after X-rays with 2 or 4 Gy. Here we showed not only p53 but also p21 protein was accumulated after X-irradiation which leads to an arrest of the cell cycle.To investigate the mechanism of p53 protein accumulation, cells were treated with several protein kinase inhibitors before X-irradiation and incubated for 2 hours. We found that quercetin could suppress the accumulation of p53 but calphostin-C had no effect. Pre-treatment of wortmannin also inhibited p53 protein accumulation and its suppressive effect was observed with only 1 minute of the treatment. Our results suggest that several pathways depend on X-ray dose are responsible for the accumulation of p53 protein and that protein kinase(s) rather than PKC is responsible for transduction of the X-ray induced signal to p53 protein.