有机氯农药与肿瘤相关基因DNA间的作用机制研究  

Spectrometric Study on Interactions between Organochlorine Pesticides and DNA

作　　者：鲁嘉[1] 卜晓阳[2] 王静[1] 李卉卉[1] 杨小弟[1] 

机构地区：[1]江苏省生物医药功能材料协同创新中心,江苏省新型动力电池重点实验室,江苏省生物功能材料重点实验室,南京师范大学化学与材料科学学院,中国经济研究中心,南京210097 [2]皖南医学院药学系,芜湖241001

出　　处：《分析化学》2014年第4期482-488,共7页Chinese Journal of Analytical Chemistry

基　　金：国家自然科学基金(No.20902048);水利部公益性行业科研专项经费项目(No.201201018);皖南医学院中青年科研基金(No.WK201315);江苏高校优势学科建设工程资助项目~~

摘　　要：利用紫外可见(UV-vis)吸收光谱、荧光(FL)光谱和圆二色谱(CD)研究了3种有机氯农药[DDT,DDE和DDD]与人类肿瘤相关基因(p53 DNA和C-myc DNA)的相互作用,阐明有机氯农药的基因毒性。UV-vis和FL光谱实验表明,有机氯农药主要通过嵌插方式与DNA碱基作用,形成非共价复合物。通过FL实验得到的农药分子与p53 DNA的结合能力顺序为:DDE>DDT>DDD,对C-myc DNA为:DDD>DDE>DDT;并通过计算结合过程的热力学常数证实以疏水作用为主要的作用力。CD实验表明,部分有机氯农药能够影响DNA的碱基对堆积和二级结构,很可能进一步造成DNA损伤,并最终导致基因突变。Abstract To clarify the genotoxicity of organochlorine pesticides, the techniques of ultraviolet and visible absorption spectrum, fluorescence （FL） spectrum and circular dichroism （CD） spectrum were used to study the interaction of DDD, DDT, DDE with tumor related gene （p53 gene and C-myc gene）. The experimental results of UV-vis absorption spectrum and FL spectrum indicated that the binding mode of organochlorine pesticides with DNA was mainly through intercalative mode to form the non-covalent compounds, leading to the reduction of stability of DNA with double helix. Using FL experiments, the order of binding affinity of pesticides and p53 DNA was DDE 〉 DDT 〉 DDD. For C-myc DNA, it was DDD 〉 DDE 〉 DDT. In addition, calculated thermodynamic constants confirmed that the hydrophobic action was the main interaction force. The result of CD indicated that parts of the organochlorine pesticides could affect the base stacking and secondary structure of DNA, which would further cause damage to DNA and ultimately lead to mutations.

关 键 词：有机氯农药 脱氧核糖核酸 相互作用 光谱法 嵌插作用 

分 类 号：TQ450.1[化学工程—农药化工] O657.3[理学—分析化学]