Cytotoxicity and apoptosis-inducing activity of bisphenol A and hydroquinone in HL-60 cells.
Cytotoxicity and apoptosis-inducing activity of bisphenol A and hydroquinone in HL-60 cells.
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DOI：
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发表时间：
2005-05
影响因子：
2
通讯作者：
H. Terasaka;Y. Kadoma;H. Sakagami;S. Fujisawa
中科院分区：
文献类型：
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作者：
H. Terasaka;Y. Kadoma;H. Sakagami;S. Fujisawa
BPA(双酚A或2，2-双(4-羟基苯酚)丙烷)和对苯二酚(HQ，1，4-苯二酚)存在于牙科树脂材料中，少量这些物质可以从树脂中洗脱出来。最近，BPA和HQ的雌激素样和致癌副作用引起了人们的关注。因此，研究这些化合物的细胞毒性和诱导细胞凋亡活性具有重要意义。BPA和HQ以浓度依赖的方式减少人早幼粒细胞白血病(HL-60)、人口腔鳞状细胞癌(HSC-2)和人颌下腺(HSG)细胞系的存活细胞数。加入N-乙酰-L-半胱氨酸(NAC)后，HQ的细胞毒活性显著降低，但双酚A的细胞毒活性无明显变化。在BPA或HQ氧化过程中硫醇的促氧化/抗氧化活性的仿生研究中，采用诱导期方法研究了BPA或HQ与2-巯基-1-甲基咪唑(MMI，一种硫醇)的混合物清除自由基的活性。没有MMI的BPA表现出比HQ更长的诱导期(抗氧化活性)，但含有MMI的BPA没有引起氧摄取。相反，HQ和MMI引起氧摄取，提示在HQ氧化过程中形成MMI硫基自由基，随后与分子氧反应。这表明HQ可能产生细胞内的活性氧(ROS)，并为NAC降低HQ的细胞毒性提供了一个解释。双酚A仅在HL-60细胞中诱导核小体间DNA断裂，这是一种凋亡的生化标志。BPA激活caspase-9和caspase-3，提示通过caspase招募结构域激活caspase而诱导细胞凋亡。BPA的细胞毒性比HQ低2倍，而诱导细胞凋亡的活性比HQ低10倍。
BPA (bisphenol A or 2,2-bis(4-hydroxy-phenol)propane) and hydroquinone (HQ, 1,4-benzenediol) are present in dental resin materials, and small quantities of these substances may be eluted from the resins. Recently, attention has focused on the estrogen-like and carcinogenic adverse effects of BPA and HQ. Thus, it is important to investigate the cytotoxicity and apoptosis-inducing activity of these compounds. BPA and HQ reduced the viable cell number of human promyelocytic leukemia (HL-60), human oral squamous cell carcinoma (HSC-2) and human submandibular gland (HSG) cell lines in a concentration-dependent manner. The cytotoxic activity of HQ, but not of BPA, was significantly reduced by the addition of N-acetyl-L-cysteine (NAC). In biomimetic studies of the prooxidant/antioxidant activity of thiols during oxidation of BPA or HQ, the radical-scavenging activities of mixtures of BPA or HQ and 2-mercapto-1-methylimidazole (MMI, a thiol) were investigated by the induction period method. BPA without MMI showed a higher induction period (antioxidant activity) than did HQ, but BPA with MMI did not cause oxygen uptake. In contrast, HQ with MMI caused oxygen uptake, suggesting formation of MMI thiyl radicals during oxidation of HQ followed by reaction with molecular oxygen. This indicates that HQ may produce intracellular reactive oxygen species (ROS) and provides an explanation for the decrease in the cytotoxicity of HQ by NAC. BPA induced internucleosomal DNA fragmentation, a biochemical marker of apoptosis, only in HL-60 cells. BPA activated caspase-9 and caspase-3, suggesting induction of apoptosis via caspase activation by the caspase recruitment domain. The cytotoxicity of BPA was 2-fold less than that of HQ, whereas the apoptosis-inducing activity of BPA was 10-fold less than that of HQ.