Sensitivity to low-dose/low-LET ionizing radiation in mammalian cells harboring mutations in succinate dehydrogenase subunit C is governed by mitochondria-derived reactive oxygen species.
Sensitivity to low-dose/low-LET ionizing radiation in mammalian cells harboring mutations in succinate dehydrogenase subunit C is governed by mitochondria-derived reactive oxygen species.
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DOI：
10.1667/rr2220.1
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发表时间：
2011-02
影响因子：
3.4
通讯作者：
Spitz DR
中科院分区：
文献类型：
--
作者：
Aykin-Burns N;Slane BG;Liu AT;Owens KM;O'Malley MS;Smith BJ;Domann FE;Spitz DR
据推测，电离辐射引起的线粒体O2代谢中断导致细胞内超氧化物（O2·−）和过氧化氢（H2 O2）稳态水平的持续可遗传性增加，这有助于辐射的生物效应。在编码线粒体电子传递链蛋白琥珀酸脱氢酶亚基C（SDHC）的基因中表达突变的成纤维细胞（B 9细胞）表现出稳态O2·−和H2 O2水平的增加。当B 9细胞暴露于低剂量/低LET辐射（5-50 cGy）时，与亲本细胞相比，它们显示出显着增加的克隆形成细胞杀伤。来源于过表达野生型人SDHC的B 9细胞（T4，T8）的克隆在暴露于5-50 cGy后相对于B 9载体对照显示出显著增加的存活分数。此外，预处理与聚乙二醇结合的铜锌超氧化物歧化酶和过氧化氢酶，以及腺病毒介导的过表达的MnSOD和/或靶向过氧化氢酶的B 9细胞暴露于10 cGy的电离辐射相对于载体对照组的生存率显着增加。腺病毒介导的MnSOD或靶向过氧化氢酶单独过表达与两者结合时同样有效。这些结果表明，过表达SDHC突变的哺乳动物细胞表现出低剂量/低LET辐射致敏作用，这是由O2·−和H2 O2水平升高介导的。这些结果也支持了线粒体O2·−和来源于SDH的H2 O2能够在低剂量电离辐射诱导的生物反应中发挥作用的假设。
It has been hypothesized that ionizing radiation-induced disruptions in mitochondrial O2 metabolism lead to persistent heritable increases in steady-state levels of intracellular superoxide (O2•−) and hydrogen peroxide (H2O2) that contribute to the biological effects of radiation. Hamster fibroblasts (B9 cells) expressing a mutation in the gene coding for the mitochondrial electron transport chain protein succinate dehydrogenase subunit C (SDHC) demonstrate increases in steady-state levels of O2•− and H2O2. When B9 cells were exposed to low-dose/low-LET radiation (5–50 cGy), they displayed significantly increased clonogenic cell killing compared with parental cells. Clones derived from B9 cells overexpressing a wild-type human SDHC (T4, T8) demonstrated significantly increased surviving fractions after exposure to 5–50 cGy relative to B9 vector controls. In addition, pretreatment with polyethylene glycol-conjugated CuZn superoxide dismutase and catalase as well as adenoviral-mediated overexpression of MnSOD and/or mitochondria-targeted catalase resulted in significantly increased survival of B9 cells exposed to 10 cGy ionizing radiation relative to vector controls. Adenoviral-mediated overexpression of either MnSOD or mitochondria-targeted catalase alone was equally as effective as when both were combined. These results show that mammalian cells over expressing mutations in SDHC demonstrate low-dose/low-LET radiation sensitization that is mediated by increased levels of O2•− and H2O2. These results also support the hypothesis that mitochondrial O2•− and H2O2 originating from SDH are capable of playing a role in low-dose ionizing radiation-induced biological responses.
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影响因子：
64.8
作者：
Ishii, N;Fujii, M;Suzuki, K
通讯作者：
Suzuki, K
影响因子：
5.3
作者：
Guo, GZ;Yan-Sanders, Y;Li, JJ
通讯作者：
Li, JJ
DOI：
10.1007/bf01542725
发表时间：
1976-01-01
期刊：
SOMATIC CELL GENETICS
影响因子：
--
作者：
CHASIN, LA;URLAUB, G
通讯作者：
URLAUB, G
影响因子：
3.4
作者：
Cromheecke, M;Piers, BA;Hoekstra, HJ
通讯作者：
Hoekstra, HJ
影响因子：
4.7
作者：
Clutton, SM;Townsend, KMS;Wright, EG
通讯作者：
Wright, EG