Alzoubi Karem H, Khabour Omar F, Jaber Aya G, Al-Azzam Sayer I, Mhaidat Nizar M, Masadeh Majed M
Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, 22110, Jordan,
Cytotechnology. 2014 May;66(3):449-55. doi: 10.1007/s10616-013-9597-8. Epub 2013 Jun 13.
Vorinostat is a member of histone deacetylase inhibitors, which represents a new class of anticancer agents for the treatment of solid and hematological malignancies. Studies have shown that these drugs induce DNA damage in blood lymphocytes, which is proposed to be due to the generation of oxidative lesions. The increase in DNA damage is sometimes associated with risk of developing secondary cancer. Thus, finding a treatment that limits DNA damage caused by anticancer drugs would be beneficial. Tempol is a potent antioxidant that was shown to prevent DNA damage induced by radiation. In this study, we aimed to investigate the harmful effects of vorinostat on DNA damage, and the possible protective effects of tempol against this damage. For that, the spontaneous frequency of sister chromatid exchanges (SCEs), chromosomal aberrations (CAs), and 8-hydroxy-2-deoxy guanosine (8-OHdG) levels were measured in cultured human lymphocytes treated with vorinostat and/or tempol. The results showed that vorinostat significantly increases the frequency of SCEs, CAs and 8-OHdG levels in human lymphocytes as compared to control. These increases were normalized by the treatment of cells with tempol. In conclusion, vorinostat is genotoxic to lymphocytes, and this toxicity is reduced by tempol. Such results could set the stage for future studies investigating the possible usefulness of antioxidants co-treatment in preventing the genotoxicity of vorinostat when used as anticancer in human.
伏立诺他是组蛋白去乙酰化酶抑制剂的一种，它代表了一类用于治疗实体瘤和血液系统恶性肿瘤的新型抗癌药物。研究表明，这些药物会在血液淋巴细胞中诱导DNA损伤，据推测这是由于氧化性损伤的产生。DNA损伤的增加有时与患继发性癌症的风险相关。因此，找到一种能限制抗癌药物引起的DNA损伤的治疗方法将是有益的。Tempol是一种有效的抗氧化剂，已被证明能预防辐射诱导的DNA损伤。在本研究中，我们旨在研究伏立诺他对DNA损伤的有害影响，以及Tempol对这种损伤可能的保护作用。为此，我们在经伏立诺他和/或Tempol处理的培养人淋巴细胞中测量了姐妹染色单体交换（SCE）的自发频率、染色体畸变（CA）和8-羟基-2-脱氧鸟苷（8-OHdG）水平。结果表明，与对照组相比，伏立诺他显著增加了人淋巴细胞中SCE、CA的频率和8-OHdG水平。用Tempol处理细胞可使这些增加恢复正常。总之，伏立诺他对淋巴细胞具有遗传毒性，而Tempol可降低这种毒性。这些结果可为未来研究抗氧化剂联合治疗在预防伏立诺他作为抗癌药物在人体使用时的遗传毒性方面的潜在用途奠定基础。
