NASA, Lyndon B. Johnson Space Center, Space Radiation Program, 2101 NASA Parkway, Mail Code SK, Houston, TX 77058, USA.
USRA Division of Life Sciences, Houston, TX 77058, USA.
Mutat Res. 2010 May 1;687(1-2):49-53. doi: 10.1016/j.mrfmmm.2010.01.012. Epub 2010 Jan 18.
Non-targeted effects (NTE), including bystander effects in neighbor cells of cells directly hit by radiation tracks and genomic instability in the progeny of irradiated cells, challenge traditional radiation protection paradigms on Earth. It is thus of interest to understand how NTE could impact our understanding of cancer risks from galactic cosmic rays (GCR), which are comprised of high-energy protons and heavy ions. The most comprehensive data set for tumor induction by heavy ions is the induction of Harderian gland tumors in mice by high-energy protons, helium, neon, iron and niobium ions after doses of 0.05 to several Gy. We report on an analysis of these data that compares a dose response model motivated by the conventional targeted effects (TE) model to one which includes a dose response term descriptive of non-targeted effects (NTE) in cell culture. Results show that a NTE model provides an improved fit to the Harderian gland data over the TE model. Relative biological effectiveness (RBE) factors are shown to have much larger values at low doses based on a NTE model than the maximum RBE estimates based on estimates of the ratio of initial linear slopes of heavy ions compared to gamma-rays in the TE model. Our analysis provides important in vivo support for the deviation from linear dose responses at low doses for high LET radiation, which are best explained by a NTE model.
非靶向效应（NTE），包括受辐射轨迹直接击中的细胞的邻细胞中的旁观者效应和辐射细胞后代中的基因组不稳定性，对地球上传统的辐射防护范式提出了挑战。因此，了解 NTE 如何影响我们对来自银河宇宙射线（GCR）的癌症风险的理解是很有意义的，GCR 由高能质子和重离子组成。重离子诱导肿瘤的最全面数据集是高能质子、氦、氖、铁和铌离子在 0.05 至数 Gy 剂量下诱导小鼠哈德氏腺肿瘤。我们报告了对这些数据的分析，该分析将由传统靶向效应（TE）模型驱动的剂量反应模型与一个包括描述细胞培养中非靶向效应（NTE）的剂量反应项的模型进行了比较。结果表明，与 TE 模型相比，NTE 模型为哈德氏腺数据提供了更好的拟合。基于 NTE 模型，相对生物效应（RBE）因子在低剂量下的值比 TE 模型中基于重离子与γ射线初始线性斜率比的最大 RBE 估计值大得多。我们的分析为低剂量下高 LET 辐射的线性剂量反应偏离提供了重要的体内支持，这最好用 NTE 模型来解释。
