Zhang Xing, Sands Mia, Lin Mindy, Guelfo Jennifer, Irudayaraj Joseph
Department of Bioengineering, University of Illinois, Urbana-Champaign, Urbana, IL 61801, USA.
Department of Civil, Environmental, and Construction Engineering, Texas Tech University, Lubbock, TX 79409, USA.
Toxicol Rep. 2024 Mar 1;12:280-288. doi: 10.1016/j.toxrep.2024.02.008. eCollection 2024 Jun.
We evaluate the cytotoxicity, intracellular redox conditions, apoptosis, and methylation of / upon exposure to LiTFSI, a novel Per and Polyfluoroalkyl Substances (PFAS) commonly found in lithium-ion batteries, on human renal carcinoma cells (A498) and hepatoma cells (HepG2). The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay showed both Perfluorooctane sulfonate (PFOS) and Lithium bis(trifluoromethanesulfonyl)imide (LiTFSI) had a dose-dependent effect on A498 and HepG2, with LiTFSI being less toxic. Intracellular redox conditions were assessed with a microplate reader and confocal, which showed a significant decrease in Reactive Oxygen Species (ROS) levels and an increase in Superoxide dismutase (SOD) content in both cells. Exposure to LiTFSI enhanced cell apoptosis, with HepG2 being more susceptible than A498. Quantitative analysis of mRNA expression levels of 19 genes associated with kidney injury, methylation, lipid metabolism and transportation was performed. LiTFSI exposure impacted kidney function by downregulating smooth muscle alpha-actin ( and upregulating transforming growth factor beta 1 (, B-cell lymphoma 2-like 1) , hepatitis A virus cellular receptor 1 (, nuclear factor erythroid 2-like 2 (, and hairy and enhancer of split 1 ( expression. LiTFSI exposure also affected the abundance of transcripts associated with DNA methylation by the expression of ten-eleven translocation ( and DNA methyltransferase ( genes. Furthermore, LiTFSI exposure induced an increase in lipid anabolism and alterations in lipid catabolism in HepG2. Our results provide new insight on the potential role of a new contaminant, LiTFSI in the regulation of oxidative stress, apoptosis and methylation in human renal carcinoma and hepatoma cells.
我们评估了新型全氟和多氟烷基物质（PFAS）双三氟甲烷磺酰亚胺锂（LiTFSI）（常见于锂离子电池中）对人肾癌细胞（A498）和肝癌细胞（HepG2）的细胞毒性、细胞内氧化还原状态、细胞凋亡及甲基化情况。MTT（3-[4,5-二甲基噻唑-2-基]-2,5-二苯基溴化四氮唑）试验表明，全氟辛烷磺酸（PFOS）和双三氟甲烷磺酰亚胺锂（LiTFSI）对A498和HepG2细胞均有剂量依赖性影响，其中LiTFSI的毒性较小。使用酶标仪和共聚焦显微镜评估细胞内氧化还原状态，结果显示两种细胞中的活性氧（ROS）水平均显著降低，超氧化物歧化酶（SOD）含量增加。暴露于LiTFSI会增强细胞凋亡，其中HepG2比A498更敏感。对与肾损伤、甲基化、脂质代谢和转运相关的19个基因的mRNA表达水平进行了定量分析。LiTFSI暴露通过下调平滑肌α-肌动蛋白（α-SMA）和上调转化生长因子β1（TGF-β1）、B细胞淋巴瘤2样1（Bcl-2L1）、甲型肝炎病毒细胞受体1（HAVCR1）、核因子红细胞2样2（Nrf2）和毛状分裂增强子1（Hes1）的表达来影响肾功能。LiTFSI暴露还通过十一-易位酶（TET）和DNA甲基转移酶（DNMT）基因的表达影响与DNA甲基化相关的转录本丰度。此外，LiTFSI暴露导致HepG2细胞中脂质合成增加，脂质分解发生改变。我们的研究结果为新型污染物LiTFSI在调节人肾癌细胞和肝癌细胞氧化应激、细胞凋亡及甲基化方面的潜在作用提供了新的见解。
