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

1.辐射诱导的P53依赖和非P53依赖的细胞凋亡及碳离子束的RBE：本研究的目的是探讨P53状态与辐射诱导的细胞凋亡的关系。用200千伏X射线或碳离子束(290 MeV/u，6 cm SOBP，NIRS)照射雄性小鼠(C57BL/6)和裸鼠移植瘤。辐射敏感的正常组织和含有野生型P53的肿瘤细胞的凋亡率显著增加(P53依赖的凋亡)，而具有突变型P53的放射抗性肿瘤细胞的凋亡率略有增加(P53依赖的凋亡)。对于具有突变型P53的抗辐射肿瘤，碳离子束的RBE值建议大于4，对于具有野生型P53的放射敏感性肿瘤，其RBE值约为3；对于具有野生型P53的正常组织(睾丸的精原细胞、小肠的隐窝细胞和海马神经细胞)，碳离子束的RBE值被建议大于4。以睾丸慢性改变为评价指标的RBE值为1.2~1.6。这些结果表明，重离子束比X射线诱导更多的非依赖于P53的细胞凋亡，肿瘤和正常组织的RBE值的差异可能有助于在放射治疗中获得有利的治疗率。2.放射治疗人类肿瘤的放射治疗：放射治疗对人类肿瘤(恶性淋巴瘤、生殖细胞瘤等)的治疗效果。并对放射治疗的疗效进行了重新评估。

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.