摘要
目的探讨不同浓度的四溴双酚A(TBBPA)和四氯双酚A(TCBPA)对人源肝癌细胞系Huh7细胞的影响机制,评估其健康风险。方法将Huh7细胞暴露于10 ng/L、100 ng/L、1000 ng/L浓度的TBBPA和TCBPA溶液中进行实验,与空白Huh7细胞进行比较,通过细胞增殖活性测定、脂滴观察、基因表达分析和转录组测序评估细胞毒性及基因表达变化。结果10 ng/L浓度下,TBBPA和TCBPA促进Huh7细胞增殖,增殖活性分别为117.3%±1.4%、127.6%±1.5%;1000 ng/L浓度下,TBBPA和TCBPA导致Huh7细胞中脂滴增加,TBBPA促使Huh7细胞晚期凋亡比例上升至11.3%±0.5%,TCBPA促使早期凋亡比例上升至8.0%±0.4%。转录组测序显示,TBBPA和TCBPA分别调控149个和171个关键基因,其中LDLR、HSD17B7、NSDHL和CREB3L3基因表达显著上调,显著影响脂质代谢通路和类固醇生物合成通路。结论TBBPA和TCBPA在高浓度下对Huh7细胞具有显著毒性,影响脂质代谢并诱导细胞凋亡。研究为评估双酚A替代品的安全性提供了科学依据,提示其潜在健康风险。
Objective To investigate the mechanism of action of different concentrations of tetrabromobisphenol A(TBBPA)and tetrachlorobisphenol A(TCBPA)on human liver cancer cell line Huh7,and to assess their health risks.Methods Huh7 cells were exposed to TBBPA and TCBPA solutions at concentrations of 10 ng/L,100 ng/L,and 1000 ng/L,and compared with blank Huh7 control cells.Cell proliferation activity,lipid droplet observation,gene expression analysis,and transcriptome sequencing were used to evaluate cytotoxicity and gene expression changes.Results At a concentration of 10 ng/L,TBBPA and TCBPA promoted Huh7 cell proliferation,and the proliferation activity was(117.3±1.4)%and(127.6±1.5)%,respectively;at a concentration of 1000 ng/L,TBBPA and TCBPA lead to an increase in lipid droplets in Huh7 cells,and TBBPA increased the proportion of late stage apoptosis in Huh7 cells to(11.3±0.5)%,while TCBPA increased the proportion of early stage apoptosis to(8.0±0.4)%.Transcriptome sequencing showed that TBBPA and TCBPA respectively regulated 149 and 171 key genes,among which the genes LDLR,HSD17B7,NSDHL,and CREB3L3 were significant upregulated,significantly affecting lipid metabolism and steroid biosynthesis pathways.Conclusion TBBPA and TCBPA have significant toxicity to Huh7 cells at high concentrations,affecting lipid metabolism and inducing cell apoptosis.This study provides a scientific basis for evaluating the safety of bisphenol A substitutes and suggests the potential health risks of these substitutes.
作者
夏祯祎
陈彬
李晓燕
袁宏霞
刘佳
李彦
XIA Zhenyi;CHEN Bin;LI Xiaoyan;YUAN Hongxia;LIU Jia;LI Yan(Department of Thoracic Surgery,Chongqing University Three Gorges Hospital,Chongqing 404000,China;Health Management Center,Chongqing University Three Gorges Hospital,Chongqing 404000,China;College of Environment and Ecology,Chongqing University,Chongqing 404000,China)
出处
《转化医学杂志》
2025年第6期121-128,共8页
Translational Medicine Journal
基金
重庆市自然科学项目(CSTB2023NSCQ-MSX0849)
重庆市万州区科研项目(wzstc20230314)。
关键词
四溴双酚A
四氯双酚A
细胞毒理学
脂质代谢
Tetrabromobisphenol A
Tetrachlorobisphenol A
Cytotoxicity
Lipid metabolism
作者简介
夏祯祎,硕士研究生,主治医师。主要从事肿瘤代谢、环境内分泌干扰物方向研究;通信作者:李彦,E-mail:wewin@163.com。
