Ligase4修复他莫昔芬诱导人类淋巴母细胞DNA损伤的机制
Mechanism of Ligase4 mediates Tamoxifen-induced DNA damage repair in TK6 cells
作者：程子圆;刘昊;卿勇;
Author：
收稿日期： 年卷（期）页码：2020,35(01):-32-36
期刊名称：华西药学杂志
Journal Name：WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字：他莫昔芬;致癌性;基因毒性;人类淋巴母细胞;DNA损伤;DNA修复;DNA双链断裂(DSBs);Ligase4;非同源末端连接(NHEJ)
Key words：
基金项目：
中文摘要
目的研究他莫昔芬(TAM)诱导人类淋巴母细胞(TK6细胞)DNA损伤的机制。方法采用MTT法检测TAM对TK6细胞活性的影响;采用免疫荧光分析和染色体畸变试验研究TAM对TK6细胞的DNA损伤作用。结果 TAM对TK6细胞的存活率呈剂量依赖性抑制,与野生型细胞(WT)比较,敲除Ligase4基因的细胞(Ligase4~(-/-))对TAM呈现出高度敏感性;与阴性对照组比较,TK6细胞经TAM处理后形成了明显增多的DNA损伤;Ligase4~(-/-)与WT比较,形成了显著增多的DNA损伤。结论 TAM可以诱导TK6细胞产生DNA损伤,Ligase4参与了TAM诱导的DNA损伤修复。
参考文献
[1] Bray F,Ferlay J,Soerjomataram I,et al.Global cancer statistics 2018:GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J].CA Cancer J Clin,2018,68(6):394-424.
[2] 王阳,齐庆涛.芹黄素联合紫杉醇对人乳腺癌MCF-7细胞株增殖、迁移及凋亡的影响[J].华西药学杂志,2015,30(1):51-53.
[3] 刘让如,陈德梅,黄艳,等.他莫昔芬磁性微球的制备及体外评价[J].华西药学杂志,2012,27(3):250-252.
[4] Poirier MC,Schild LJ.The genotoxicity of tamoxifen:Extent and consequences,Kona,Hawaii,January 23,2003[J].Mutagenesis,2003,18(4):395-399.
[5] Chapman JR,Taylor MRG,Boulton SJ.Playing the end game:DNA double-strand break repair pathway choice [J].Mol Cell,2012,47(4):497-510.
[6] 王杏林,尹东东,张俊伟.依托泊苷口服微乳的制备及质量评价[J].华西药学杂志,2009,24(2):139-141.
[7] Hu X,Wu X,Liu H,et al.Genistein-induced DNA damage is repaired by nonhomologous end joining and homologous recombination in TK6 cells [J].J Cell Physiol,2018,234(3):2683-2692.
[8] Mah LJ,El-Osta A,Karagiannis TC.γH2AX:A sensitive molecular marker of DNA damage and repair [J].Leukemia,2010,24(4):679-686.
[9] 胡晓青,刘颖,卿勇.白藜芦醇诱导DT40细胞DNA损伤的机制研究[J].华西药学杂志,2018,33(1):31-33.
[10] Phillips DH.Understanding the genotoxicity of tamoxifen?[J].Carcinogenesis,2001,22(6):839-849.
[11] Mizutani A,Okada T,Shihutani S,et al.Extensive chromosomal breaks are induced by tamoxifen and estrogen in DNA repair-deficient cells[J].Cancer Res,2004,64(9):3144-3147.
[12] Zafar MK,Eoff RL.Translesion DNA synthesis in cancer:Molecular mechanisms and therapeutic opportunities[J].Chem Res Toxicol,2017,30(11):1942-1955.
【关闭】
