HIF-1α高表达对苯代谢物诱导K562细胞毒性的影响

doi:10.3969/j.issn.1004-616x.2018.01.009

癌变·畸变·突变 ›› 2018, Vol. 30 ›› Issue (1): 47-51,57.doi: 10.3969/j.issn.1004-616x.2018.01.009

HIF-1α高表达对苯代谢物诱导K562细胞毒性的影响

孙凤霞, 孟醒, 孙蓉丽, 张娟, 尹立红, 浦跃朴

东南大学公共卫生学院环境医学工程教育部重点实验室, 江苏南京 210009

收稿日期:2017-09-28 修回日期:2018-01-07 出版日期:2018-01-30 发布日期:2018-01-30
通讯作者: 浦跃朴,E-mail:yppu@seu.edu.cn E-mail:yppu@seu.edu.cn
作者简介:孙凤霞,E-mail:fxsun7@outlook.com。
基金资助:
国家自然科学基金资助项目（81573189，81730087）

Relationship between expression of HIF-1α and cytotoxicity from exposure to benzene metabolites on K562 cells

SUN Fengxia, MENG Xing, SUN Rongli, ZHANG Juan, YIN Lihong, PU Yuepu

Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, Jiangsu, China

Received:2017-09-28 Revised:2018-01-07 Online:2018-01-30 Published:2018-01-30

摘要/Abstract

摘要： 目的：研究缺氧诱导因子-1α（HIF-1α）高表达对苯代谢物1，4-苯醌、氢醌、苯酚诱导K562细胞毒性的影响。方法：用不同浓度的1，4-苯醌（0、10、20、40、80 μmol/L）、氢醌（0、10、20、40、80 μmol/L）、苯酚（0、1、1.5、2、2.5、5 mmol/L）分别染毒对照组K562细胞及高表达HIF-1α的K562细胞24 h，MTT法检测细胞增殖情况，PI/FITC Annxein V双染结合流式细胞术检测细胞凋亡率，碘化丙啶结合流式细胞术检测细胞周期。结果：MTT实验结果显示，1，4-苯醌染毒后，两株细胞均出现增殖率下降且呈剂量效应关系，1，4-苯醌浓度为80 μmol/L时，高表达HIF-1α的K562细胞增殖率高于对照组K562细胞（P < 0.05）。氢醌和苯酚在较高浓度染毒后，对照组K562细胞亦出现增殖抑制，而高表达HIF-1α的K562细胞增殖无明显抑制。流式细胞术结果显示，1，4-苯醌染毒后，两株细胞的细胞凋亡率增加且呈剂量效应关系。20 μmol/L浓度1，4-苯醌染毒时，高表达HIF-1α的K562细胞较对照组K562细胞凋亡减弱（P < 0.05）。氢醌和苯酚染毒后，两株细胞的凋亡率与未染毒组比较，差异均无统计学意义（P均 > 0.05），高表达HIF-1α的K562细胞的凋亡率较对照组K562细胞亦无显著差异。细胞周期检测结果显示，3种苯代谢物均可引起K562细胞周期阻滞在G0/G1期或S期。结论：3种苯的代谢物中，1，4-苯醌对K562细胞的毒性大于氢醌和苯酚，HIF-1α高表达可降低苯代谢物引起的细胞毒性，其作用的发挥可能是通过调节细胞增殖及凋亡而实现。

关键词: HIF-1α, 苯代谢物, 细胞增殖, 细胞凋亡, 细胞周期

Abstract: OBJECTIVE: To study the effects of expression of HIF-1α on cytotoxicity of K562 cells induced by 1,4-benzoquinone (1,4-BQ),hydroquinone (HQ) and phenol. METHODS: The control K562 cells (K-c) and K562 cells with high expression of HIF-1α (K-h) were treated with different concentrations of 1,4-BQ (0,10,20,40,80 μmol/L),HQ (0,10,20,40,80 μmol/L) and phenol (0,1,1.5,2,2.5,5 mmol/L) for 24 h. Cell proliferation was detected by MTT assay,apoptosis was detected by flow cytometry with PI/FITC Annxein V double staining,and cell cycle was detected by propidium iodide combined with flow cytometry. RESULTS: The MTT results revealed that the relative proliferation rate of K-c cells and K-h cells showed a dose-related decrease after treating with 1,4-BQ (P < 0.05). The relative proliferation rate of K-h was higher than control K-c (P < 0.05) in 80 μmol/L 1,4-BQ. After treating with HQ and phenol at higher concentrations,K-c exhibited proliferation inhibition,while no significant proliferation inhibition was observed in K-h. Flow cytometry results revealed that the apoptosis rate increased in K-c and K-h (P < 0.05) and showed a dose-response relationship after exposuring to 1,4-BQ for 24 h (P < 0.05). Moreover,the apoptosis rate of K-hwas lower than K-c (P < 0.05) with 20 μmol/L 1,4-BQ. After exposure to HQ and phenol,K-c and K-h demonstrated no significant differences compared with control group,K-h was not significantly different from K-c. The results of cell cycle analysis demonstrated K-c were arrested in G0/G1 phase or S-phase after exposure to 1,4-BQ,HQ and phenol. CONCLUSION: Among benzene metabolites,1,4-BQ was the most cytotoxic,followed by HQ and phenol. High expression of HIF-1α reduced the cytotoxicity of K562 cell caused by benzene metabolites,and HIF-1α might work in regulating cell proliferation,apoptosis through cell cycle control.

Key words: HIF-1α, benzene metabolites, proliferation, apoptosis, cell cycle

中图分类号:

R994.6

孙凤霞, 孟醒, 孙蓉丽, 张娟, 尹立红, 浦跃朴. HIF-1α高表达对苯代谢物诱导K562细胞毒性的影响[J]. 癌变·畸变·突变, 2018, 30(1): 47-51,57.

SUN Fengxia, MENG Xing, SUN Rongli, ZHANG Juan, YIN Lihong, PU Yuepu. Relationship between expression of HIF-1α and cytotoxicity from exposure to benzene metabolites on K562 cells[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2018, 30(1): 47-51,57.

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HIF-1α高表达对苯代谢物诱导K562细胞毒性的影响

Relationship between expression of HIF-1α and cytotoxicity from exposure to benzene metabolites on K562 cells

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