A structure-based investigation on the binding interaction of hydroxylated polycyclic aromatic hydrocarbons with DNA | |
Wang, Li-Rong ; Wang, Ying ; Chen, Jing-Wen ; Guo, Liang-Hong | |
刊名 | TOXICOLOGY
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2009-08-21 | |
卷号 | 262期号:3页码:250-257 |
关键词 | Hydroxylated polycyclic aromatic hydrocarbons DNA Electrochemistry Binding interaction QSAR |
中文摘要 | Binding of polycyclic aromatic hydrocarbons (PAHs) with DNA is one of the key steps in their mutagenic process. In this work, a previously established electrochemical displacement method was utilized to measure the binding constants (K(b)) of 26 hydroxylated PAHs (OH-PAHs) with DNA. Eighteen OH-PAHs induced more than 50% signal reduction in the displacement measurement with calf thymus DNA, and K(b) calculated from the EC(50) value is between 8.3 x 10(4) and 3.0 x 10(5) M(-1). Other eight OH-PAHs induced less than 50% signal reduction. For the latter compounds, EC50 values were obtained by fitting the displacement curve with a bi-exponential decay function and extrapolating it to 50% signal. K(b) was then calculated, and was found to be in the range of 4.5 x 10(4) and 7.6 x 10(4) M(-1). Measurements with polydG.polydC (pdGC) and polydA.polydT (pdAT) demonstrate that the OH-PAHs have no obvious selectivity toward DNA base pairs. In atomic force microscopy, a clear morphological change of calf thymus DNA from linear type to condensation form was observed after binding with 9-hydroxyfluorene. The change is similar to the one observed with the DNA-intercalating electrochemical indicator, suggesting that 9-hydroxyfluorene binds with DNA also by intercalation. An examination of the relationship between the molecular structure characteristics of the 26 OH-PAHs and their DNA-binding affinity revealed that the most positive net atomic charge on a hydrogen atom (q(H)(+)) correlated significantly with K(b) at 0.05 level, with sig. (2-tailed) of 0.015. The correlation suggests that hydrogen bonding may play an important role in DNA/OH-PAH binding interaction. It was further revealed that Connolly accessible area (CAA), Connolly molecular area (CMA), and Connolly solvent-excluded volume (CSEV) of the nine hydroxybenzo[a]pyrenes correlated significantly with K(b) at 0.01 or 0.05 level, with sig. (2-tailed) 0.019, 0.012 and 0.009, implying that steric effect might be an important factor in the binding of differently substituted OH-PAH with DNA. (C) 2009 Elsevier Ireland Ltd. All rights reserved. |
WOS记录号 | WOS:000269287700011 |
内容类型 | 期刊论文 |
源URL | [http://ir.rcees.ac.cn/handle/311016/21448] ![]() |
专题 | 生态环境研究中心_环境化学与生态毒理学国家重点实验室 |
推荐引用方式 GB/T 7714 | Wang, Li-Rong,Wang, Ying,Chen, Jing-Wen,et al. A structure-based investigation on the binding interaction of hydroxylated polycyclic aromatic hydrocarbons with DNA[J]. TOXICOLOGY,2009,262(3):250-257. |
APA | Wang, Li-Rong,Wang, Ying,Chen, Jing-Wen,&Guo, Liang-Hong.(2009).A structure-based investigation on the binding interaction of hydroxylated polycyclic aromatic hydrocarbons with DNA.TOXICOLOGY,262(3),250-257. |
MLA | Wang, Li-Rong,et al."A structure-based investigation on the binding interaction of hydroxylated polycyclic aromatic hydrocarbons with DNA".TOXICOLOGY 262.3(2009):250-257. |
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