Genetic changes in progeny of bystander human fibroblasts after microbeam irradiation with X-rays, protons or carbon ions: The relevance to cancer risk
Genetic changes in progeny of bystander human fibroblasts after microbeam irradiation with X-rays, protons or carbon ions: The relevance to cancer risk
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DOI：
10.3109/09553002.2014.950715
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发表时间：
2015-01-01
影响因子：
2.6
通讯作者：
Suzuki, Masao
中科院分区：
文献类型：
--
作者：
Autsavapromporn, Narongchai;Plante, Ianik;Suzuki, Masao
目的：辐射引起的旁观者效应对放射治疗具有重要影响。它们在正常细胞中的持续存在可能会增加健康危害的风险，包括癌症。本研究探讨了辐射质量和间隙连接细胞间通讯 (GJIC) 在旁观者细胞后代中有害影响传播中的作用。 材料和方法：汇合的人类皮肤成纤维细胞暴露于具有不同线性能量转移 (LET) 的微束辐射，平均吸收剂量为 0.4 Gy，其中 0.036-0.4% 的细胞直接受到辐射靶向。经过 20 次群体倍增后，收获细胞并检测微核形成、基因突变和蛋白质氧化。结果：我们的结果表明，旁观者细胞后代中应激效应的表达依赖于 LET。暴露于 X 射线（LET 类似于 6 keV/μ m）或质子（LET 类似于 11 keV/mm）的旁观者细胞的后代表现出持续的氧化应激，这与次黄嘌呤鸟嘌呤磷酸核糖基转移酶（HPRT）基因座的微核形成和突变增加相关。在碳离子（LET 类似于 103 keV/mm）照射后没有观察到这种效应。有趣的是，在 GJIC 受到抑制的条件下，暴露于质子或碳离子的培养物中的旁观者细胞的后代具有减少的氧化和遗传损伤。当培养物暴露于 X 射线时，没有检测到这种缓解作用。结论：这些发现表明，细胞暴露于质子和重带电粒子（具有与此处使用的类似的 LET 特性）可以降低与癌症相关的病变的风险。辐射时细胞通过间隙连接进行通讯的能力似乎会影响旁观者细胞后代的残余损伤。
Purpose: Radiation-induced bystander effects have important implications in radiotherapy. Their persistence in normal cells may contribute to risk of health hazards, including cancer. This study investigates the role of radiation quality and gap junction intercellular communication (GJIC) in the propagation of harmful effects in progeny of bystander cells.Materials and methods: Confluent human skin fibroblasts were exposed to microbeam radiations with different linear energy transfer (LET) at mean absorbed doses of 0.4 Gy by which 0.036-0.4% of the cells were directly targeted by radiation. Following 20 population doublings, the cells were harvested and assayed for micronucleus formation, gene mutation and protein oxidation.Results: Our results showed that expression of stressful effects in the progeny of bystander cells is dependent on LET. The progeny of bystander cells exposed to X-rays (LET similar to 6 keV/mu m) or protons (LET similar to 11 keV/mm) showed persistent oxidative stress, which correlated with increased micronucleus formation and mutation at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus. Such effects were not observed after irradiation by carbon ions (LET similar to 103 keV/mm). Interestingly, progeny of bystander cells from cultures exposed to protons or carbon ions under conditions where GJIC was inhibited harbored reduced oxidative and genetic damage. This mitigating effect was not detected when the cultures were exposed to X-rays.Conclusions: These findings suggest that cellular exposure to proton and heavy charged particle with LET properties similar to those used here can reduce the risk of lesions associated with cancer. The ability of cells to communicate via gap junctions at the time of irradiation appears to impact residual damage in progeny of bystander cells.