Evaluation of vitamin B12 effects on DNA damage induced by paclitaxel
Evaluation of vitamin B12 effects on DNA damage induced by paclitaxel
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DOI：
10.3109/01480545.2013.851686
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发表时间：
2014-07-01
影响因子：
2.6
通讯作者：
Al-Azzam, Sayer
中科院分区：
文献类型：
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作者：
Alzoubi, Karem;Khabour, Omar;Al-Azzam, Sayer
紫杉醇 (PAC) 是一种抗癌药物，已被证明会产生自由基，导致不可逆的细胞损伤。维生素 B12 具有抗氧化特性，可以保护 DNA 免受自由基的侵害。在这项研究中，我们研究了 PAC 对 DNA 可能的遗传毒性作用以及维生素 B12 对紫杉醇引起的 DNA 损伤可能的保护作用。在用 PAC (10 μM) 和/或维生素 B12 (2.7 mg/mL) 处理的培养人血淋巴细胞中测量姐妹染色单体交换 (SCE)、染色体畸变 (CA) 和 8-羟基-2'-脱氧鸟苷 (8-OHdG) 水平。我们的结果表明，与对照组相比，PAC 显着增加了人血液淋巴细胞中 SCE (p < 0.001) 和 CA (p < 0.001) 的频率。这些由 PAC 药物引起的 DNA 损伤可以通过用维生素 B12 预处理细胞来预防。此外，我们还发现 PAC 会诱导 8-OHdG（DNA 氧化损伤的标志物）增加，而维生素 B12 可以阻止这种增加。维生素 B12 似乎可以防止人类血液淋巴细胞中 PAC 引起的遗传毒性。
Paclitaxel (PAC) is an anticancer drug that has been shown to generate free radicals leading to irreversible cell injury. Vitamin B12 has antioxidative properties and can protect DNA from free radicals. In this study, we examined the possible genotoxic effect of PAC on DNA as well as the possible protective effect of vitamin B12 on DNA damage induced by paclitaxel. Sister chromatid exchanges (SCEs), chromosomal aberrations (CAs) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were measured in cultured human blood lymphocytes treated with PAC (10 mu M) and/or vitamin B12 (2.7 mg/mL). Our results showed that PAC significantly increased the frequencies of SCEs (p < 0.001) and CAs (p < 0.001) in human blood lymphocytes, as compared to controls. These DNA damages, caused by PAC drug, were prevented by pretreatment of cells with vitamin B12. In addition, we showed that PAC induced an increase in 8-OHdG, a marker of oxidative DNA damage, and that this increase was prevented by vitamin B12. Vitamin B12 seems to protect against genotoxicity induced by PAC in human blood lymphocytes.