苯并[a]芘和1-羟基芘诱导人胚胎干细胞分化心肌细胞ROS、CYP基因表达和DNA损伤  

Benzo[a]pyrene and 1-Hydroxypyrene Induce ROS,CYP Gene Expression and DNA Damage in Human Embryonic Stem Cell Derived Cardiomyocytes

作　　者：吴彬彬[1,2] 晏斌 胡梅 陈曦 梁岩[5] Wu Binbin;Yan Bin;Hu Mei;Chen Xi;Liang Yan(Shenzhen Institutes of Advanced Technology,Chinese Academy of Sciences,Shenzhen 518055,China;University of Chinese Academy of Sciences,Beijing 100049,China;LKS Faculty of Medicine,The University of Hong Kong,Hong Kong,China;Shandong Institute for Food and Drug Control,Ji’nan 250101,China;School of Resources and Environment,University of Electronic Science and Technology of China,Chengdu 611731,China)

机构地区：[1]中国科学院深圳先进技术研究院,深圳518055 [2]中国科学院大学,北京100049 [3]香港大学李嘉诚医学院,中国香港 [4]山东省食品药品检验研究院,济南250101 [5]电子科技大学资源与环境学院,成都611731

出　　处：《生态毒理学报》2020年第2期96-103,共8页Asian Journal of Ecotoxicology

基　　金：广东省科技计划项目(2016A020214015);电子科技大学科研启动基金资助项目(Y03019023601008022);中国科学院战略性先导科技专项(XDA20060303)。

摘　　要：多环芳烃(PAHs)化合物中的苯并[a]芘和PAHs暴露检测标志物1-羟基芘与心脏功能障碍有关,但其生物学机制尚不清楚。为研究苯并[a]芘和1-羟基芘对心脏的毒性作用,基于人胚胎干细胞分化心肌细胞(hESC-CM)研究了苯并[a]芘和1-羟基芘对心肌细胞活性氧(ROS)生成、CYP基因表达和DNA损伤等的影响。结果表明,苯并[a]芘和1-羟基芘对h ESC-CM活性无影响,但能显著增强细胞ROS水平,诱导DNA损伤。此外,苯并[a]芘还能诱导细胞线粒体促凋亡基因的表达。研究表明,苯并[a]芘和1-羟基芘能通过诱导氧化应激和DNA损伤事件导致h ESC-CM损伤,在一定程度上解释了多环芳烃暴露导致心脏疾病的分子机制。Benzo[a]pyrene,as a carcinogenic polycyclic aromatic hydrocarbon(PAH)compound,has received great concern due to its high health risk.1-hydroxypyrene,a metabolite of pyrene,is widely used as one biomarker for PAHs.Previous studies demonstrated that both benzo[a]pyrene and 1-hydroxypyrene related with cardiac dysfunction,but the biological mechanisms have remained unclear.In the present study,toxic mechanisms of these two PAHs were evaluated using human embryonic stem cell derived cardiomyocytes(hESC-CM).The results showed that both benzo[a]pyrene and 1-hydroxypyrene enhanced the intracellular level of ROS and induced DNA damage.Benzo[a]pyrene also induced an expression of cell mitochondrial proapoptotic gene.Overall,the oxidative stress and DNA damage contributed to PAHs toxicity in cardiomyocytes and probably associated with heart diseases.

关 键 词：多环芳烃 胚胎干细胞分化心肌细胞 DNA损伤 

分 类 号：X171.5[环境科学与工程—环境科学]