Grillo C A, Dulout F N
Centro de Investigaciones en Genética Básica y Aplicada (CIGEBA), Facultad de Ciencias Veterinarias Universidad Nacional de La Plata, 1900 La Plata, Argentina.
Mutagenesis. 2006 Nov;21(6):405-10. doi: 10.1093/mutage/gel046. Epub 2006 Oct 25.
Previous reports showed the protective effect of the synthetic antioxidant butylated hydroxytoluene (BHT) against the chromosomal damage induced by bleomycin (BLM), cadmium chloride and potassium dichromate. To test the hypothesis that this effect was exerted by inhibition and/or scavenging of reactive oxygen species (ROS), the effect of BHT on the chromosomal damage induced by a high dose-rate gamma rays (HDR (192)Ir). Experiments were carried out by irradiating G(1) CHO cells with nominal doses of 1, 2 or 3 Gy. BHT (doses of 1.0, 2.5 or 5.0 microg/ml) was added to the culture immediately before or immediately after irradiation. Cells were then incubated in the presence of BHT for 13 h until harvesting and fixation. Results obtained showed that BHT did not decrease the chromosomal damage induced by radiation in any consistent fashion. On the contrary, in cells post-treated with 5.0 microg/ml of BHT the yield of chromosomal aberrations increased in several experimental points. These results with ionizing radiation suggest that the previous observed protective effects of BHT on the chromosomal damage induced by chemical genotoxicants may not be mediated solely through the scavenging or inactivating reactive oxidative species. The decrease of the yield of chromosomal damage induced by BLM could be due to the union of BHT with a metallic ion, in this case Fe (II), required for the activation of BLM. In the same way, the protective effect of BHT on the chromosomal damage induced by cadmium chloride and potassium dichromate could be due to the decrease of the effective dose of both salts in the cell through the chelation of the cations by BHT.
先前的报告显示，合成抗氧化剂丁基羟基甲苯（BHT）对博来霉素（BLM）、氯化镉和重铬酸钾诱导的染色体损伤具有保护作用。为了验证这种作用是通过抑制和/或清除活性氧（ROS）来实现的这一假设，研究了BHT对高剂量率γ射线（HDR (192)Ir）诱导的染色体损伤的影响。实验通过用1、2或3 Gy的标称剂量照射G(1)期中国仓鼠卵巢（CHO）细胞来进行。在照射前或照射后立即向培养物中加入BHT（剂量为1.0、2.5或5.0 μg/ml）。然后将细胞在BHT存在下孵育13小时，直至收获和固定。所得结果表明，BHT并未以任何一致的方式降低辐射诱导的染色体损伤。相反，在用5.0 μg/ml BHT进行后处理的细胞中，在几个实验点染色体畸变率增加。这些关于电离辐射的结果表明，先前观察到的BHT对化学遗传毒性剂诱导的染色体损伤的保护作用可能并非仅通过清除或灭活活性氧化物质来介导。BLM诱导的染色体损伤率降低可能是由于BHT与激活BLM所需的金属离子（在这种情况下为Fe (II)）结合。同样，BHT对氯化镉和重铬酸钾诱导的染色体损伤的保护作用可能是由于BHT螯合阳离子从而降低了细胞中两种盐的有效剂量。
