中文摘要：

【摘要】目的观察氢醌诱导体外细胞DNA甲基化水平改变，探讨聚ADP-核糖聚合酶l[poly（ADP．ribose）polymerasel，PARPll在该过程中的作用。方法以10、20、40、60、80μmol／L浓度的氢醌分别处理人支气管皮细胞（16HBE）及其PARPl缺陷细胞（16HBE—shPARP1）48h，对照组加入等体积的PBS溶液。采用高效毛细管电泳检测基因组DNA整体甲基化水平，检测PARP1和DNA甲基转移酶1（DNAmethvltransferases1，DNMT1）mRNA表达的变化。结果16HBE和16HBE．shPARPl细胞基因组整体甲基化百分比（mCpG％）分别为（4．89％±O．07％）和（9．53％±0．51％）。经5．氮杂脱氧胞苷（DAC）处理72h后，mCpG％值分别下降为（3．07％±0．12％）和（6．34％±0．3％），经单因素方差分析，2种细胞不同处理组mCpG％的差异有统计学意义（F值为61．25和60．36，均P〈0．01）。16HBE细胞各氢醌染毒组的PARPImRNA相对表达分别为对照组的145．0％、159．0％、169．0％、215．0％和236．0％，差异均有统计学意义（P〈0．01）；16HBE．shPARPl细胞，各氢醌染毒组PARPlmRNA相对表达水平分别为对照组的170．0％、223．0％、264．0％、327．0％和320．0％，差异均有统计学意义（P〈0．01）。当氢醌染毒剂量达到20、40、60、80μmol／L，16HBE细胞DNMT1mRNA相对表达水平分别为对照组的114．0％、126．0％、136．0％和162．0％，差异有统计学意义（均P〈0．01）；当氢醌染毒剂量达10、20、40、60、80μmol／L，16HBE—shPARPl细胞DNMT]mRNA相对表达水平分别为对照组的141．0％、165．2％、186．9％、202．1％和217．3％，差异有统计学意义（P〈0．01）。结论氢醌能引起16HBE细胞低甲基化，PARP1可通过影响DNMT1的表达及改变DNMT1的活性来调节16HBE细胞DNA甲基化改变。

英文摘要：

Objective To investigate the DNA methylation changes induced by hydroquinone （HQ） in human bronchial epithelial cells and to explore the role of poly （ADP-ribose） polymerase-1 （PARP-I） in this process. Methods Human bronchial epithelial 16HBE cells and PARP-l-deficient 16HBE cells （ 16HBE-shPARP-1 cells） were exposed to HQ （10, 20, 40, 60, and 80 p, mol/L） for48 h, while control cells were treated with an equal volume of PBS solution. The changes in genomic DNA metbylation were investigated by high-performance capillary electrophoresis, and the expression levels of PARP-1 and DNA methyhransferase 1 （DNMT1） were measured. Results The percentages of methylated DNA of overall genome （mCpG%） in 16HBE and 16HBE-shPARP-1 cells were 4.89%＋0.07% and 9.53%＋0.51%, respectively; after treatment with 5-aza-2＇-deoxycitidine for 72 h, mCpG% decreased to 3.07~0.12% and 6.34%~0.3%, respectively. The one-way analysis of variance revealed significant differences in mCpG% between the cells exposed to different concentrations of HQ in both 16HBE and 16HBE-shPARP-1 groups （F=61.25, P〈0.01; F=60.36, P〈0.O1 ）. For 16HBE ceils treated with HQ （ 10, 20, 40, 60, and 80 p~mol/L）, the mRNA expression levels of PARP-1 were 145.0%, 159.0%, 169.0%, 215.0%, and 236.0%, respectively, compared with those in the control group, with significant differences （P〈0.01 for all）, for 16HBE-shPARP-I cells treated with HQ （10, 20, 40, 60, and 80 p~mol/L）, the mRNA expression levels of PARP-1 were 170.0%, 223.0%, 264.0%, 327.0%, and 320.0%, respectively, compared with those in the control group, with significant differences （P〈0.01 for all）. When the dose of HQ reached 20, 40, 60, and 80 p~mol/ L, the mRNA expression levels of DNMT1 in 16HBE group were 114.0%, 126.0%, 136.0%, and 162.0%, respectively, compared with those in the control group, with significant differences （P〈0.01 for all）; when the dose of HQ reached 10, 20, 40, 60, and 80 p.mol/L, the mRNA expression levels of DNMT1 in the