Changeinradiation sensitivityby mitochondrial damageand their mechanisms

线粒体损伤引起的辐射敏感性变化及其机制

• 批准号: 12671844
• 负责人: MAJIMA Hideyuki
• 金额: $ 2.05万
• 依托单位: Kagoshima University (2001)National Institute of Radiological Sciences (2000)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671844/
• 关键词: Radiation; Apoptosis; Mitochondria; Sensitivity; Manganese SOD; 致死機構; 活性酸素

We observed previously that mitochondria DNA-less (Rho 0) cells are much more sensitive to radiation in terms of the radiationsensitivity (colony assay), apoptosis (Hoechst stain), DNA double strand breaks, and chromosome aberrations. An other finding is that Rho 0 cells contain much less amount of manganese superoxidedismutase (MnSOD) in themitochondria. A transfection vector containing MnSOD was made and was transfected to the Rhocells, and the change in apoptosis frequency was observed. The results showed that frequency of apoptosis by X-irradiation was decreased compared to that in the non-transfected cells, suggesting the MnSOD is a factor to determine the radiation sensitivity. These results indicate that changes in mitochondrial factors play an important key-role in determination of the radiation sensitivity. These evidences were also confirmed by transfecting to an other cell line, HLE, a hepatocarcinoma cell line, by transfecting the MnSOD gene containingvectors. These results suggest that change in superoxide levels in mitochondria is an important factor to determine the cellular radiation sensitivity.

我们之前观察到，线粒体DNA-less （Rho 0）细胞在辐射敏感性（菌落测定）、细胞凋亡（Hoechst染色）、DNA双链断裂和染色体畸变方面对辐射更敏感。另一项发现是，Rho 0细胞线粒体中锰超氧化物歧化酶（MnSOD）的含量要少得多。制备含有MnSOD的转染载体，转染Rhocells，观察细胞凋亡频率的变化。结果显示，与未转染的细胞相比，x照射下细胞凋亡频率降低，提示MnSOD是决定辐射敏感性的一个因素。这些结果表明，线粒体因子的变化在辐射敏感性的测定中起着重要的关键作用。这些证据也被转染到另一个细胞系，HLE，肝癌细胞系，转染含有MnSOD基因的载体。这些结果表明，线粒体超氧化物水平的变化是决定细胞辐射敏感性的重要因素。

项目成果

馬嶋秀行, 本告成淳, 山口千鶴, 柿沼志津子, 平井太, 鈴木雅雄, 小澤俊彦, 安藤興一, 藤高和信: "放射線障害に対する細胞内ミトコンドリアの役割"癌の臨床. 第47号,第1号. 14-16 (2001)

Hideyuki Majima、Jun Honjo、Chizuru Yamaguchi、Shizuko Kakinuma、Futoshi Hirai、Masao Suzuki、Toshihiko Ozawa、Koichi Ando、Kazunobu Fujitaka：《细胞内线粒体在放射损伤中的作用》第 47 期，第 1 期。 14-16 (2001)

Hideyuki J.Majima et al.: "Complex-type chromosal exchanges in blood lymphocytes during radiation therapy correlate with acute toxicity"Cancer Letters. 150. 215-222 (2000)

Hideyuki J.Majima 等人：“放射治疗期间血液淋巴细胞中的复杂型染色体交换与急性毒性相关”《癌症快报》。

Ando K, Furusawa Y, Suzuki M, Nojima K, Majima H, Koike S, Aoki M, Shimizu W, Futami Y, Ogino T, Murayama S, Ikeda H: "Relative Biological Effectiveness of the 235 MeV proton beams at the National Cancer Hospital East"J. Radiat. Res.. 42. 79-89 (2001)

Ando K、Furusawa Y、Suzuki M、Nojima K、Majima H、Koike S、Aoki M、Shimizu W、Futami Y、Ogino T、Murayama S、Ikeda H：“235 MeV 质子束在国家癌症中心的相对生物有效性

Yamada,S., Durante,M., Ando,K., Furusawa,Y., Kawata,T., Majima,H., Tsujii,H.: "Complex-type chromosomal exchanges in blood lymphocytes during radiation therapy correlate with acute toxicity"Cancer Lett.. 150. 215-221 (2000)

Yamada,S., Durante,M., Ando,K., Furusawa,Y., Kawata,T., Majima,H., Tsujii,H.：“放射治疗期间血液淋巴细胞中的复杂型染色体交换与急性

Motoori S, Majima HJ, Ebara M, Kato H, Hirai F, Kakinuma S, Yamaguchi C, Ando K, Ozawa T, Nagano T, Tsujii H, Saisho H: "Overexpression of mitochondrial manganese superoxide dismutase protects against radiation-induced cell death in the human hepatocellul

Motoori S、Majima HJ、Ebara M、Kato H、Hirai F、Kakinuma S、Yamaguchi C、Ando K、Ozawa T、Nagano T、Tsujii H、Saisho H：“线粒体锰超氧化物歧化酶的过度表达可防止辐射诱导的细胞死亡