Hickman A W, Jaramillo R J, Lechner J F, Johnson N F
Inhalation Toxicology Research Institute, Albuquerque, New Mexico 87185.
Cancer Res. 1994 Nov 15;54(22):5797-800.
Other investigators have shown that both sparsely ionizing and UV radiation cause cell cycle arrest that is associated with increased expression of wild-type p53 protein. The effect of exposure to alpha-particles from 238Pu on the induction of the p53 protein has now been examined in cultured lung epithelial cells derived from male F344 rats. The number of cells having increased levels of p53 protein was determined by flow cytometry after the cells had been stained with a monoclonal antibody to p53. alpha-Particle irradiation caused a dose-dependent increase in p53 protein levels detectable at doses as low as 0.6 cGy, with no evidence of a threshold. An increase in p53 protein also occurred in X-irradiated cells. However, no increase was seen in cells exposed to less than 10 cGy of X-rays, indicating the existence of a relatively higher DNA damage threshold for sparsely ionizing radiation. In addition, more cells exposed to low doses of alpha radiation had increased p53 protein levels than would be predicted based on the number of nuclei expected to be traversed by an alpha-particle, suggesting that alpha-particles cause genetic damage by mechanisms in addition to direct interactions with DNA.
其他研究人员已表明，低传能线密度辐射和紫外线辐射都会导致细胞周期停滞，这与野生型p53蛋白表达增加有关。现在，研究人员已在源自雄性F344大鼠的培养肺上皮细胞中检测了暴露于238Pu产生的α粒子对p53蛋白诱导的影响。在用针对p53的单克隆抗体对细胞进行染色后，通过流式细胞术确定p53蛋白水平升高的细胞数量。α粒子照射导致在低至0.6 cGy的剂量下即可检测到p53蛋白水平呈剂量依赖性增加，且无阈值迹象。X射线照射的细胞中p53蛋白也出现增加。然而，在暴露于低于10 cGy X射线的细胞中未观察到增加，这表明低传能线密度辐射存在相对较高的DNA损伤阈值。此外，暴露于低剂量α辐射的细胞中，p53蛋白水平升高的细胞比基于预期被α粒子穿过的细胞核数量所预测的更多，这表明α粒子除了通过与DNA的直接相互作用外，还通过其他机制导致遗传损伤。
