Department of Radiology, UMDNJ - New Jersey Medical School Cancer Center, Newark, New Jersey 07103, USA.
Radiat Res. 2011 Apr;175(4):405-15. doi: 10.1667/RR2461.1. Epub 2011 Feb 14.
Widespread evidence indicates that exposure of cell populations to ionizing radiation results in significant biological changes in both the irradiated and nonirradiated bystander cells in the population. We investigated the role of radiation quality, or linear energy transfer (LET), and radiation dose in the propagation of stressful effects in the progeny of bystander cells. Confluent normal human cell cultures were exposed to low or high doses of 1GeV/u iron ions (LET ∼ 151 keV/µm), 600 MeV/u silicon ions (LET ∼ 51 keV/µm), or 1 GeV protons (LET ∼ 0.2 keV/µm). Within minutes after irradiation, the cells were trypsinized and co-cultured with nonirradiated cells for 5 h. During this time, irradiated and nonirradiated cells were grown on either side of an insert with 3-µm pores. Nonirradiated cells were then harvested and allowed to grow for 20 generations. Relative to controls, the progeny of bystander cells that were co-cultured with cells irradiated with iron or silicon ions, but not protons, exhibited reduced cloning efficiency and harbored higher levels of chromosomal damage, protein oxidation and lipid peroxidation. This correlated with decreased activity of antioxidant enzymes, inactivation of the redox-sensitive metabolic enzyme aconitase, and altered translation of proteins encoded by mitochondrial DNA. Together, the results demonstrate that the long-term consequences of the induced nontargeted effects greatly depend on the quality and dose of the radiation and involve persistent oxidative stress due to induced perturbations in oxidative metabolism. They are relevant to estimates of health risks from exposures to space radiation and the emergence of second malignancies after radiotherapy.
广泛的证据表明，细胞群体暴露于电离辐射会导致辐射和非辐射旁观者细胞发生重大的生物学变化。我们研究了辐射质量（或线性能量传递（LET））和辐射剂量在旁观者细胞后代中传播应激效应的作用。将汇合的正常人细胞培养物暴露于低剂量或高剂量的 1GeV/u 铁离子（LET ∼ 151 keV/µm）、600 MeV/u 硅离子（LET ∼ 51 keV/µm）或 1 GeV 质子（LET ∼ 0.2 keV/µm）。在照射后几分钟内，将细胞用胰蛋白酶消化并与非照射细胞共培养 5 小时。在此期间，将照射和未照射的细胞在带有 3-µm 孔的插入物的两侧生长。然后收获非照射细胞并允许其生长 20 代。与对照相比，与用铁或硅离子照射的细胞共培养的旁观者细胞的后代表现出克隆效率降低，并且携带更高水平的染色体损伤、蛋白质氧化和脂质过氧化。这与抗氧化酶活性降低、氧化还原敏感代谢酶 aconitase 失活以及线粒体 DNA 编码的蛋白质翻译改变有关。总之，这些结果表明，诱导的非靶向效应的长期后果在很大程度上取决于辐射的质量和剂量，并涉及由于氧化代谢的诱导扰动而导致的持续氧化应激。它们与从太空辐射暴露和放射治疗后第二恶性肿瘤的出现中估计健康风险有关。
