Mechanisms of Mitochondrial Cell Death Induced by Radiation

辐射诱导线粒体细胞死亡的机制

• 批准号: 10671786
• 负责人: MAJIMA Hideyuki
• 金额: $ 0.77万
• 依托单位: National Institute of Radiological Science
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671786/
• 关键词: Radiation; Apoptosis; Mitochondria; Mechanisms of Cell Death; Free Radical; Sensitivity; Vitamin E; 染色体異常; 生存率; DNA2重鎖切断

Mitochondrial DNA codes 13 components of electron transport chain. Lacking of mtDNA abrogates the electron transport system. We hypothesize that mitochondria deficient in functional electron transport system can result in increased production of superoxide and thus more oxidative stress. Sensitivity to X-rays, clonogenicity, frequency of double strand breaks(DSB), chromosome aberration, free radical generation, apoptosis and oxidative damage markers were examined in 143B human oseteosarcoma cell line (Rho+) and mtDNA-less (Rho0) cells derived from this cell line. No significant difference was observed between Rho+ and Rho0 cells without X-rays exposure for frequency of DSB and chromosome aberration. Clonogenicity assay showed greater sensitivity in Rho0 cells compared to Rho+ cells exposed to X-rays. More DSBs, and more chromosome aberrations in terms of gap, translocation, and deletion were observed in Rho0 cells. Substitution of normal mitochondria including mitochondrial DNA resulted recover of X-ray sensitivity. These results suggest that Rho0 cells lacking mtDNA has more oxidative stress and higher sensitivity to X-rays. Furthermore, the chromosomal damage by irradiation was restored substantially by Vitamin E.

线粒体 DNA 编码电子传递链的 13 种成分。线粒体 DNA 的缺乏会导致电子传递系统失效。我们假设线粒体功能电子传递系统的缺陷会导致超氧化物的产生增加，从而导致更多的氧化应激。在 143B 人骨肉瘤细胞系 (Rho+) 和源自 143B 人骨肉瘤细胞系 (Rho+) 和无 mtDNA (Rho0) 细胞中检查对 X 射线的敏感性、克隆性、双链断裂频率 (DSB)、染色体畸变、自由基生成、细胞凋亡和氧化损伤标记物该细胞系。在没有 X 射线照射的情况下，Rho+ 和 Rho0 细胞之间的 DSB 频率和染色体畸变没有观察到显着差异。克隆形成分析显示，与暴露于 X 射线的 Rho+ 细胞相比，Rho0 细胞具有更高的敏感性。在 Rho0 细胞中观察到更多的 DSB 以及更多的染色体畸变（如缺口、易位和缺失）。包括线粒体 DNA 在内的正常线粒体的替代导致 X 射线敏感性的恢复。这些结果表明，缺乏线粒体DNA的Rho0细胞具有更多的氧化应激和对X射线的更高敏感性。此外，维生素 E 可以显着恢复辐射造成的染色体损伤。

项目成果

Measurements of the equivalent whole-body dose during radiation therapy by cytogenetic methods

• DOI: 10.1088/0031-9155/44/5/314
• 发表时间: 1999-05-01
• 期刊: PHYSICS IN MEDICINE AND BIOLOGY
• 影响因子: 3.5
• 作者: Durante, M;Yamada, S;Tsujii, H
• 通讯作者: Tsujii, H

Mutations in the promoter reveal a cause for the reduced expression of the human manganese superoxide dismutase gene in cancer cells.

启动子突变揭示了癌细胞中人锰超氧化物歧化酶基因表达减少的原因。

• DOI: 10.1038/sj.onc.1202265
• 发表时间: 1999
• 期刊: Oncogene.
• 作者: Xu,Y;Krishnan,A;Wan,XS;Majima,H;Yeh,CC;Ludewig,G;Kasarskis,EJ;StClair,DK
• 通讯作者: StClair,DK

Hideyuki J.Majima et al.: "Association Between G2-phase block and radiation-induced chromosome fragment repair in human lymphocytes"Radiat.Res.. 151. 670-676 (1999)

Hideyuki J.Majima 等：“人类淋巴细胞中 G2 期阻滞与辐射诱导的染色体片段修复之间的关联”Radiat.Res.. 151. 670-676 (1999)

Koichi Ando et al.: "X-rays vs.carbon-ion tumor therapy : Measurements of the equivalent whole-body dose during radiation therapy by cytogenetic methods"Phys.Med.Biol.. 44. 1289-1298 (1999)

Koichi Ando 等人：“X 射线与碳离子肿瘤治疗：通过细胞遗传学方法测量放射治疗期间的等效全身剂量”Phys.Med.Biol.. 44. 1289-1298 (1999)

Theoretical strategy : How to make treatment planning for heavy ion-beam therapy?

理论策略：重离子束治疗如何制定治疗计划？

• 发表时间: 1999
• 期刊: Jpn.J.Med.Phys. 19
• 作者: Majima HJ;Suzuki M;Ando K;Sakata K;Suzuki N;Okada S;Suzuki S;Miyamoto T;Fujitaka K;Fujii H;Yamada S;Tsujii H;Urano M
• 通讯作者: Urano M