Radiation-induced p53-independent apoptosis and radiosensitivity in human tumors

1.p53依赖性和非p53依赖性辐射诱导的细胞凋亡及碳离子束的放射损伤效应：本研究旨在探讨p53状态与辐射诱导的细胞凋亡的关系。用200 kV X射线或碳离子束（290 MeV/u，6 cm SOBP，NIRS）照射雄性小鼠（C57 BL/6）和裸鼠移植瘤。放射敏感的正常组织和具有野生型p53的肿瘤细胞的凋亡的发生率在放射后显著增加（p53依赖性凋亡），尽管具有突变型p53的放射抗性肿瘤细胞的凋亡的发生率略有增加（p53依赖性凋亡）。通过凋亡细胞死亡评价的碳离子束的RBE值表明，对于具有突变型p53的放射抗性肿瘤，RBE值大于4，对于具有野生型p53的放射敏感性肿瘤，RBE值约为3，对于具有野生型p53的放射敏感性正常组织（睾丸的精原细胞、小肠的隐窝细胞和海马的神经元细胞），RBE值为1.5-2.1。此外，根据睾丸的慢性变化评估的RBE值为1.2-1.6。这些结果表明，重离子束较X射线诱导更多的p53非依赖性细胞凋亡，肿瘤与正常组织的RBE值的差异可能有助于放射治疗的有利治疗比。2.放射敏感性肿瘤的放射治疗：放射敏感性肿瘤（恶性淋巴瘤、生殖细胞瘤等）的放射治疗结果。并重新评价放射治疗的疗效。

1.p53-dependent and p53-independent apoptosis induced by radiation, and RBE of carbon ion beams :The aim of this study is to evaluate the relationships between p53 status and radiation-induced apoptosis. Male mice (C57BL/6) and human tumors transplanted to nude mice were irradiated with 200 kV X-rays or carbon ion beams (290MeV/u, 6cm SOBP,NIRS). The incidence of apoptosis of radiosensitive normal tissues and tumor cells having wild-type p53 increased markedly following irradiation (p53-dependent apoptosis), although the incidence of apoptosis of radioresistant tumor cells having mutant-type p53 increased slightly (p53-ihdependent apoptosis). The RBE values of carbon ion beams evaluated by apoptotic cell death were suggested to be more than 4 for a radioresistant tumor having mutant-type p53, about 3 for radiosensitive tumors having wild-type p53, and 1.5-2.1 for radiosensitive normal tissues having wild-type p53 (spermoatogonia of the testis, crypt cells of the small intestine, and neuronal cells of the hippocampus). Furthermore, the RBE values evaluated by the chronic changes of the testis were 1.2-1.6. These results indicated that the heavy ion beams induce more p53-independet apoptosis than X-rays, and the differences in the RBE values between tumors and normal tissues might contribute to a favorable therapeutic ratio in radiotherapy.2.Radiation therapy for radiosensitive human tumors :Treatment results of radiation therapy for radiosensitive human tumors (malignant lymphoma, germinoma, etc.) were analyzed, and the efficacy of radiation was reevaluated.