吴彬彬^1,2,
晏斌³,
胡梅⁴,
陈曦^1,2,5,
梁岩⁵
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, 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

作者简介: 吴彬彬(1988-),男,博士研究生,研究方向为环境毒理学,E-mail:bb.wu@siat.ac.cn.

基金项目: 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)


中图分类号: X171.5

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

Wu Binbin^1,2,
Yan Bin³,
Hu Mei⁴,
Chen Xi^1,2,5,
Liang Yan⁵
1. Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China;
2. University of Chinese Academy of Sciences, Beijing 100049, China;
3. LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China;
4. Shandong Institute for Food and Drug Control, Ji'nan 250101, China;
5. School of Resources and Environment, University of Electronic Science and Technology of China, Chengdu 611731, China

CLC number: X171.5

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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hESC-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hESC-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。
关键词: 多环芳烃/
胚胎干细胞分化心肌细胞/
DNA损伤

Abstract: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.
Key words:polycyclic aromatic hydrocarbon/
human embryonic stem cells derived cardiomyocytes/
DNA damage.

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