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.