通过检测受照射细胞及与其共培养旁细胞的损伤情况及p53抑制剂对其的影响,研究了肝癌细胞辐射敏感性及辐射诱导的旁效应与p53的关系。发现肝癌细胞的辐射敏感性与p53密切相关:野生型p53辐射敏感性最高,突变型的次之,缺失型的敏感性最低。同时,辐射诱导的旁效应与p53状态亦密切相关,仅野生型p53肝癌细胞(HepG2)对旁细胞(Chang氏肝细胞)具有旁效应,且未受照射旁细胞中产生的微核具有明显的剂量效应和时间效应;而突变型(PLC)和缺失型(Hep3B)的肝癌细胞几乎不能诱导辐射旁效应的产生。另外,p53抑制剂可显著抑制辐射旁效应的产生。
The role of p53 in bystander responses on normal liver cells were investigated by co-culturing irradiated hepatoma cells with non-irradiated bystander Chang liver cells. It was found that radiosensitivity of the hepatoma cells was relative to p53. HepG2 cells with wtp53 had the highest radiosensitivity followed by PLC/PRF/5 cells with mtp53 and Hep3B cells with null-p53. The induction of bystander micronucleus (MN) was observed only in the Chang liver cells that had been co-cultured with HepG2 cells but not co-cultured with PLC/PRF/5 or Hep3B. Also, this bystander MN was relative to the irradiation dose and the cell co-culture rime. When the hepatoma cells were treated with pifithfin-α, a p53 inhibitor, their radiosensitivities were reduced, and the bystander effect was diminished. The results indicate that p53 could regulate not only the radiosensitivity but also the bystander response.