低剂量氚水基于Nrf2通路诱导肺癌细胞的辐射适应性反应  

Low dose tritiated water induced radiation-adaptive responses in lung cancer cells based on the Nrf2 pathway

作　　者：丁子仪 徐照[2] 曹敬文 季涛涛 周袁媛 杨彦彦 李桃生 DING Ziyi;XU Zhao;CAO Jingwen;JI Taotao;ZHOU Yuanyuan;YANG Yanyan;LI Taosheng(Science Island Branch,Graduate School of USTC,Hefei 230026;Institute of Nuclear Energy Safety Technology,Hefei Institutes of Physical Science,Chinese Academy of Sciences,Hefei 230031;Institute of Material Science and Information Technology,Anhui University,Hefei 230601)

机构地区：[1]中国科学技术大学研究生院科学岛分院,合肥230026 [2]中国科学院合肥物质科学研究院核能安全技术研究所,合肥230031 [3]安徽大学物质科学与信息技术研究院,合肥230601

出　　处：《辐射防护》2025年第1期67-76,共10页Radiation Protection

摘　　要：本文研究了氚水在人非小细胞肺癌细胞A549中诱导辐射适应性反应及其高活度阈值,并进一步探究了Nrf2通路在氚水诱导适应性反应中的作用。设置7×103、1.4×104、2.1×104、2.8×104、3.5×104 Bq/mL五个梯度氚水活度(累计照射剂量为0.55~8.27 mGy),用氚水预处理A549细胞24 h,随后照射4 Gy X射线,用MTT检测细胞活力,显示较低活度(7×103和1.4×104 Bq/mL)氚水处理后可恢复4 Gy照射后A549细胞的细胞活力,具有适应性反应;而大于2.1×104 Bq/mL活度的氚水处理后,A549的细胞活力不再恢复,适应性反应消失,随着活度的增加,细胞活力进一步降低;鉴于1.4×104 Bq/mL的氚水诱导的适应性反应最为显著,因此,选用此活度氚水开展氧化水平的检测实验。结果显示,氚水可以显著降低X射线高剂量照射后胞内活性氧(ROS)水平,表明适应性反应受控于氧化水平;在氚水(1.4×104 Bq/mL)预处理细胞阶段加入Nrf2的抑制剂(ML385),可显著抑制氚水诱导的辐射抗性,表明抗氧化途径Nrf2参与了此过程。This study investigated the induction of radiation adaptive response and its high activity threshold by tritiated water(HTO)in human non-small cell lung cancer cells(A549).The role of the Nrf2 pathway in the induction of adaptive response by HTO was further explored.Five gradient activities of HTO(7×103,1.4×104,2.1×104,2.8×104,3.5×104 Bq/mL)were set(accumulated radiation dose ranging from 0.55 to 8.27 mGy).A549 cells were pre-treated with HTO for 24 hours,followed by irradiation with 4 Gy X-rays.Cell viability was measured using MTT assay.The results showed that lower activities of HTO(7×103 and 1.4×104 Bq/mL)could restore the cell viability of A549 cells after 4 Gy irradiation,indicating the presence of an adaptive response.However,HTO with activities higher than 2.1×104 Bq/mL resulted in no recovery of cell viability in A549 cells,indicating the disappearance of adaptive response.Moreover,with increasing activity,cell viability further decreased.Considering that the adaptive response induced by HTO with an activity of 1.4×104 Bq/mL is the most significant,this activity of HTO was selected for the detection of oxidative levels.The results showed that HTO can significantly reduce the intra-cellular reactive oxygen species(ROS)levels after high-dose X-ray irradiation,indicating that the adaptive response is regulated by oxidative levels.Moreover,the addition of Nrf2 inhibitor(ML385)during the pre-treatment stage of HTO(1.4×104 Bq/mL)can significantly inhibit the radiation resistance induced by HTO,suggesting the involvement of the antioxidant pathway Nrf2 in this process.

关 键 词：氚水 电离辐射 适应性反应 Nrf2通路 

分 类 号：Q691[生物学—生物物理学]