QSAR study on the non-monotonic dose-response curve of PCBs in chicken embryo hepatocyte bioassay  

作　　者：YunSong Mu  AiQian Zhang  ChangAn Gao  SuFen Peng LianSheng Wang 

机构地区：[1] State Key Laboratory of Pollution Control and Resource Reuse, School of Environment, Nanjing University, Nanjing, 210093, China

出　　处：《Science China Chemistry》2009年第5期662-669,共8页中国科学（化学英文版）

基　　金：Supported by the National Natural Science Foundation of China(Grant Nos. 20777035 & 20737001) ;863 Advanced Research Project (Grant Nos. 2007AA06Z416, 2006AA06Z424 & 2007AA06A405)

摘　　要：Endocrine disrupting chemicals (EDCs) in the natural environment exhibit a unique non-monotonic dose-response curve and it is impossible to select one simple index to characterize the bilogogical activity of these compounds. Quantitative structure-activity relationship (QSAR) study on non-monotonic dose-response curve has become a real challenge presently. In order to explore the possible mechanism for the non-monotonic dose-response curve of polychlorinated biphenyls congeners (PCBs) in chicken embryo hepatocyte bioassay, AM1 method of ChemOffice was adopted to calculate necessary structure descriptors for PCBs, while the interactions between PCBs and simulated AhR ligand binding domain (LBD) were analyzed by using FlexX in SYBYL7.0. Different binding modes for PCBs have been distinguished not only from aligned conformation but also from free binding energy. Some QSAR models were established separately for both low and high doses ranges, revealing that receptor binding may predominate in the interference of the physiological function of cytochrome P4501A-P4501A in the low doses range. But with the higher doses range, the EROD suppression might be related to acute toxicity owing to molecular polarity or distribution of charges and consequently damage structure and function of chicken embryo hepatocyte.Endocrine disrupting chemicals (EDCs) in the natural environment exhibit a unique non-monotonic dose-response curve and it is impossible to select one simple index to characterize the bilogogical activity of these compounds. Quantitative structure-activity relationship (QSAR) study on non-monotonic dose-response curve has become a real challenge presently. In order to explore the possible mechanism for the non-monotonic dose-response curve of polychlorinated biphenyls congeners (PCBs) in chicken embryo hepatocyte bioassay, AM1 method of ChemOffice was adopted to calculate necessary structure descriptors for PCBs, while the interactions between PCBs and simulated AhR ligand binding domain (LBD) were analyzed by using FlexX in SYBYL7.0. Different binding modes for PCBs have been distinguished not only from aligned conformation but also from free binding energy. Some QSAR models were established separately for both low and high doses ranges, revealing that receptor binding may predominate in the interference of the physiological function of cytochrome P4501A-P4501A in the low doses range. But with the higher doses range, the EROD suppression might be related to acute toxicity owing to molecular polarity or distribution of charges and consequently damage structure and function of chicken embryo hepatocyte.

关 键 词：POLYCHLORINATED BIPHENYLS CONGENERS (PCBs) non-monotonic DOSE-RESPONSE curve quantitative STRUCTURE-ACTIVITY relationship (QSAR) 

分 类 号：Q95-3[生物学—动物学]