Cemeli Eduardo, Anderson Diana
Genetic and Reproductive Toxicology Group, Division of Biomedical Sciences, University of Bradford, Bradford, West Yorkshire, BD7 1DP, UK; E-Mail:
Int J Mol Sci. 2011;12(5):2783-96. doi: 10.3390/ijms12052783. Epub 2011 Apr 28.
Past research has demonstrated that oestrogenic compounds produce strand breaks in the DNA of sperm and lymphocytes via reactive oxygen species (ROS). In the current investigation, sperm and lymphocytes were treated in vitro with oestrogenic compounds (diethylstilboestrol, progesterone, 17β-oestradiol, noradrenaline and triiodotyronine) and several aspects of DNA damage were investigated. Firstly, mediation of DNA damage by lipid peroxidation was investigated in the presence of BHA (a lipid peroxidation blocker). BHA reduced the DNA damage generated by 17β-oestradiol and diethylstilboestrol in a statistically significant manner. No effects were observed for sperm. Secondly, the presence of oxidized bases employing FPG and EndoIII were detected for lymphocytes and sperm in the negative control and after 24 h recovery in lymphocytes but not immediately after treatment for both cell types. The successful detection of oxidized bases in the negative control (untreated) of sperm provides an opportunity for its application in biomonitoring studies. DNA repair at 24 h after exposure was also studied. A nearly complete recovery to negative control levels was shown in lymphocytes 24 h recovery after oestrogenic exposure and this was statistically significant in all cases. Rapid rejoining of DNA, in a matter of hours, is a characteristic of DNA damaged by ROS.
以往的研究表明，雌激素化合物可通过活性氧（ROS）导致精子和淋巴细胞的DNA链断裂。在当前的研究中，用雌激素化合物（己烯雌酚、孕酮、17β-雌二醇、去甲肾上腺素和三碘甲状腺原氨酸）对精子和淋巴细胞进行体外处理，并对DNA损伤的几个方面进行了研究。首先，在丁基羟基茴香醚（一种脂质过氧化阻滞剂）存在的情况下，研究脂质过氧化对DNA损伤的介导作用。丁基羟基茴香醚以统计学上显著的方式减少了17β-雌二醇和己烯雌酚产生的DNA损伤。对精子未观察到影响。其次，在阴性对照以及淋巴细胞恢复24小时后，检测淋巴细胞和精子中使用FPG和EndoIII的氧化碱基的存在情况，但两种细胞类型在处理后立即未检测到。在精子的阴性对照（未处理）中成功检测到氧化碱基，为其在生物监测研究中的应用提供了机会。还研究了暴露24小时后的DNA修复情况。雌激素暴露后24小时恢复时，淋巴细胞显示几乎完全恢复到阴性对照水平，且在所有情况下这都具有统计学意义。在数小时内DNA迅速重新连接是ROS损伤DNA的一个特征。
