Aspirin potently inhibits oxidative DNA strand breaks: implications for cancer chemoprevention.
Aspirin potently inhibits oxidative DNA strand breaks: implications for cancer chemoprevention.
复制标题
阿司匹林有效抑制氧化 DNA 链断裂：对癌症化学预防的影响。
DOI：
10.1016/s0006-291x(02)00271-1
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发表时间：
2002
影响因子：
3.1
通讯作者：
Li,Yunbo
中科院分区：
文献类型：
--
作者：
Hsu,CSusan;Li,Yunbo
流行病学研究表明，阿司匹林的使用与人类恶性肿瘤，特别是结直肠癌的发病率下降有关。由于活性氧（ROS）在多阶段致癌中起着重要作用，因此本研究旨在检测阿司匹林抑制ROS介导的DNA损伤的能力。用过氧化氢（H_2O_2）+Cu（Ⅱ）和对苯二酚（HQ）+ Cu（Ⅱ）引起φX-174质粒DNA氧化性断裂。我们证明，在慢性抗炎治疗期间，与血浆中的量相容的浓度（0.5- 2 mM）的阿司匹林的存在导致对由H2 O2/Cu（II）或HQ/Cu（II）诱导的氧化DNA损伤的显著抑制。阿司匹林对DNA氧化损伤的抑制作用呈浓度依赖性。此外，阿司匹林被发现是更有效的比羟基自由基清除剂，甘露醇和二甲基亚砜，在保护对过氧化氢/铜（II）介导的DNA链断裂。由于Cu（II）还原为Cu（I）在H2 O2/Cu（II）和HQ/Cu（II）介导的羟基自由基或其等价物的形成以及随后的氧化DNA损伤中至关重要，因此我们研究了阿司匹林是否可以抑制这种Cu（II）/Cu（I）氧化还原循环。观察到对DNA氧化损伤具有抑制作用的浓度的阿司匹林不会改变H2 O2/Cu（II）或HQ/Cu（II）系统中的Cu（II）/Cu（I）氧化还原循环。此外，没有发现阿司匹林显著抑制H2 O2。这项研究首次表明，阿司匹林有效地抑制H2 O2/Cu（II）和HQ/Cu（II）介导的氧化DNA链断裂最有可能通过清除羟基自由基或其等效物来自这两个系统。阿司匹林对DNA氧化损伤的有效抑制作用可能部分有助于其在人体中观察到的抗癌活性。
Epidemiological studies have suggested that the use of aspirin is associated with a decreased incidence of human malignancies, particularly colorectal cancer. Since reactive oxygen species (ROS) are critically involved in multistage carcinogenesis, this study was undertaken to examine the ability of aspirin to inhibit ROS-mediated DNA damage. Hydrogen peroxide (H2O2)+Cu(II) and hydroquinone (HQ) + Cu(II) were used to cause oxidative DNA strand breaks in φX-174 plasmid DNA. We demonstrated that the presence of aspirin at concentrations (0.5–2mM) compatible with amounts in plasma during chronic anti-inflammatory therapy resulted in a marked inhibition of oxidative DNA damage induced by either H2O2/Cu(II) or HQ/Cu(II). The inhibition of oxidative DNA damage by aspirin was exhibited in a concentration-dependent manner. Moreover, aspirin was found to be much more potent than the hydroxyl radical scavengers, mannitol and dimethyl sulfoxide, in protecting against the H2O2/Cu(II)-mediated DNA strand breaks. Since the reduction of Cu(II) to Cu(I) is crucially involved in both H2O2/Cu(II)- and HQ/Cu(II)-mediated formation of hydroxyl radical or its equivalent, and the subsequent oxidative DNA damage, we examined whether aspirin could inhibit this Cu(II)/Cu(I) redox cycle. It was observed that aspirin at concentrations that showed the inhibitory effect on oxidative DNA damage did not alter the Cu(II)/Cu(I) redox cycle in either H2O2/Cu(II) or HQ/Cu(II) system. In addition, aspirin was not found to significantly scavenge H2O2. This study demonstrates for the first time that aspirin potently inhibits both H2O2/Cu(II)- and HQ/Cu(II)-mediated oxidative DNA strand breaks most likely through scavenging the hydroxyl radical or its equivalent derived from these two systems. The potent inhibition of oxidative DNA damage by aspirin may thus partially contribute to its anticancer activities observed in humans.