State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing, 210023, P.R. China.
Department of Environmental Science, School of Engineering, China Pharmaceutical University, Nanjing, 211198, China.
Sci Rep. 2019 Jan 14;9(1):107. doi: 10.1038/s41598-018-36455-4.
Toxicity of arsenic (As) has been widely characterized. However, few studies focus on whether cell responses induced by As at nontoxic concentration could be inherited and further change cell tolerance to another pollutant. In this study, human A549 and HeLa cells were exposed to As at nontoxic concentrations for 10 or 15 passages, then the cells were recovered in the cell medium without As. At 25th passage, residual As in both type of cells was completely removed through the recovery process. And no abnormity in cell viability was identified in both type of cells between control and As-treated groups. Above results indicated that As exposure-recovery treatment had limited influence on phenotype of the cells. However, gene expression profiles determined by high-throughput sequencing showed that As exposure-recovery treatment induced similar expression modification of genes related to inflammation, oxidative stress and epigenetic modulation in the A549 and HeLa cells after recovery of 10 or 15 passages, indicating that As-induced cellular responses have been partially memorized at transcriptional level. The memory effect might play key roles in increased tolerance of the A549 and HeLa cells to adverse effects (cell viability, intracellular reactive oxygen species (ROS) generation and plasma membrane damage) induced by titanium dioxide nanoparticles (as representative pollutant). This study shed new lights on toxic effects induced by As at nontoxic concentration, which is useful for risk assessment of combined effects of As and other pollutants.
砷（As）的毒性已得到广泛研究。然而，很少有研究关注 As 在非毒性浓度下诱导的细胞反应是否可以遗传，并进一步改变细胞对另一种污染物的耐受性。在这项研究中，用人肺腺癌细胞（A549）和人宫颈癌细胞（HeLa）分别在非毒性浓度的 As 中培养 10 或 15 代，然后在不含 As 的细胞培养液中恢复培养。在第 25 代时，通过恢复过程，两种细胞中的残留 As 被完全去除。并且在对照组和 As 处理组之间，两种细胞的细胞活力均无异常。以上结果表明，As 暴露-恢复处理对细胞表型的影响有限。然而，高通量测序确定的基因表达谱显示，经过 10 或 15 代的恢复，As 暴露-恢复处理诱导了 A549 和 HeLa 细胞中与炎症、氧化应激和表观遗传调控相关的基因表达相似的修饰，表明 As 诱导的细胞反应已在转录水平上部分被记忆。这种记忆效应可能在增加 A549 和 HeLa 细胞对二氧化钛纳米颗粒（作为代表性污染物）引起的不利影响（细胞活力、细胞内活性氧（ROS）生成和质膜损伤）的耐受性方面发挥关键作用。本研究为非毒性浓度 As 诱导的毒性作用提供了新的认识，有助于评估 As 与其他污染物联合作用的风险。
