p53-independent apoptosis, non-apoptotic programmed cell death, and organelle

(1)将人室管膜母细胞瘤、胶质母细胞瘤和小细胞肺癌移植到裸鼠皮下，用10GyX射线照射裸鼠，照射后3h、4.5h和6h切除肿瘤，制作切片，用空气中微粒子诱发X射线发射(Micro-PIXE)检测细胞死亡、凋亡和坏死等元素分布的变化。在未照射的肿瘤中，磷(P)、钾(K)、氯(C1)和硫(S)存在于存活的肿瘤细胞的胞核和胞浆中，在小的坏死灶中这些元素明显减少。室管膜母细胞瘤照射后可明显诱导细胞凋亡，但用微量PIXE很难清楚地检测到这些成分的分布变化。在胶质母细胞瘤和小细胞肺癌中，可见小的坏死性病变，P、K、Cl、S显著降低，与形态学观察结果一致。(2)人脑TU-…将更多的MORS(胶质母细胞瘤、室管膜母细胞瘤和原始神经外胚层瘤：PNET)移植到裸鼠皮下，用碳离子束(290 MeV/u，6 cm SOBP)或200kVX射线照射。照射后6小时或48小时取肿瘤、脑、脾、肾、十二指肠、睾丸称重，光镜下观察细胞凋亡及其他组织学改变。碳离子束比X射线更有效，其RBE值均大于1.0，但因肿瘤和终点的不同而不同。照射后6h，室管膜母细胞瘤细胞凋亡率碳离子照射为5~49个/高倍视野(HPF)，X射线照射为3~9个/HPF。在胶质母细胞瘤中，碳离子测定值为1.2-4.0/hpf，X射线测定值为0.4-1.0/hpf。室管膜母细胞瘤、PNET和胶质母细胞瘤的RBE值分别为3.0、3.6和6.1。而对辐射敏感的正常组织的RBE值为1.2~2.1。这些结果表明，重离子束治疗放射抵抗肿瘤比X射线更有利。较少

(1) We subcutaneously transplanted cells of human ependymoblastoma, glioblastoma, and small cell lung cancer (SCLC) into nude mice, irradiated them with 10 Gy X-ray at 200 kV, excised the tumors 3, 4.5, or 6 hours after irradiation, produced sections, and examined the changes in the distribution of elements by cell death, apoptosis and necrosis, using an in-air micro-particle-induced X-ray emission (micro-PIXE). In the non-irradiated tumors, phosphorus (P), potassium (K), chlorine (C1), and sulfur (S) were observed in the nuclei and cytoplasm of viable tumor cells, and these elements were significantly decreased in small necrotic lesions. In ependymoblastoma, apoptosis was markedly induced after irradiation, but it was difficult to clearly detect the changes in the distribution of these elements by the micro-PIXE. In glioblastoma and SCLC, small necrotic lesions were observed, and P, K, Cl, and S were significantly decreased, agreeing well with morphological findings.(2) Human brain tu … More mors (glioblastoma, ependymoblastoma, and primitive neuroectodermal tumor : PNET) were transplanted to nude mice subcutaneously, and the mice were irradiated with carbon ion beams (290MeV/u, 6cm SOBP) or 200kV X-rays. Tumors, brains, spleens, kidneys, duodenums, and testes were excised and weighed 6 or 48 hours after irradiation, and they were microscopically examined to evaluate apoptosis and other histological changes. Carbon ion beams were more effective than X-rays and the RBE values were more than 1.0, but the values varied according to the tumors and endpoints. The incidences of apoptosis 6 hours after 0.25-1 Gy irradiation were 5-49/high power field (HPF) by carbon ion and 3-9/HPF by X-ray in the ependymoblastoma. Those values were 1.2-4.0/HPF by carbon ion and 0.4-1.0/HPF by X-ray in the glioblastoma. RBE values were 3.0, 3.6, and 6.1 for the ependymoblastoma, the PNET, and the glioblastoma, respectively. In contrast, RBE values of radiosensitive normal tissues were 1.2-2.1. These results suggest that the heavy ion beams are more favorable for treating radioresistant tumors than X-rays. Less