游离脂肪酸和铁的组合诱导哺乳动物细胞HPRT突变与线粒体功能障碍（英文）  

Combination of free fatty acid and iron induces HPRT mutation and mitochondrial dysfunction in mammalian cells

作　　者：詹鹰[1] 于海兵 刘曌宇[3] 丁婷[3] 李敏[1] 李华文 丁元林 刘正湘[1,3] 孔丹莉 姚大纯[1,2] 

机构地区：[1]华中科技大学同济文昌医院,海南文昌571321 [2]广东医科大学公共卫生学院,广东东莞523808 [3]华中科技大学同济医学院附属同济医院内科,湖北武汉430030

出　　处：《广东医学院学报》2016年第3期217-224,共8页Journal of Guangdong Medical College

基　　金：国家自然科学基金项目(No.81273166)

摘　　要：目的游离脂肪酸可与铁结合并转运铁进入细胞,而人们对游离脂肪酸与铁诱发的突变和DNA损伤的潜在协同作用知之甚少。方法该文研究了铁和游离脂肪酸的协同毒性作用,在成纤维细胞中通过HPRT基因突变测量其潜在致突变作用,并通过8羟基脱氧鸟苷的形成测量对DNA的损伤。同时还研究了铁和游离脂肪酸介导的线粒体功能障碍。结果结果发现铁和游离脂肪酸的组合在成纤维细胞中有明显的协同毒性作用,而单独的铁和游离脂肪酸不显示任何影响。铁和游离脂肪酸的组合能明显增加活性氧自由基的产生,产生显著的HPRT突变,DNA损伤,以及线粒体功能障碍。结论游离脂肪酸和铁可以发挥协同的细胞毒性,在哺乳动物细胞中增加活性氧自由基的产生,导致HPRT突变,DNA损伤与线粒体功能障碍。由于与铁的协同毒性作用,游离脂肪酸对人体健康可能是一个潜在的危险因素。Objective Free fatty acid （FFA） can bind with iron and translocate it into cells, while little is known about their potential synergistic effect on mutagenesis and DNA damage. Methods After treated with iron and/or FFA, cytotoxicity, reactive oxygen species （ORS） level, HPRT mutation, DNA damage and mitochondrial function of human fibroblast cell line NF1604 were determined. Results The combination of iron and FFA yielded a synergistic toxic effect on NF1604 cells, but iron or FFA did not. Iron plus FFA increased the ROS generation and induced HPRT mutation, DNA damage and mitochondrial dysfunction. Conclusion Both FFA and iron can exert a synergistic cytotoxicity to mammalian cells via upregulation of ROS production and lead to HPRT mutation and DNA damage with mitochondrial dysfunction. FFA may be a potential risk factor to human health due to its synergistic cytotoxicity with iron.

关 键 词：游离脂肪酸 铁 突变 线粒体 活性氧自由基. 

分 类 号：R589.2[医药卫生—内分泌]