Study on the mechanism of action between dimethyl phthalate and herring sperm DNA at molecular level

ABSTRACT

Dimethyl phthalate (DMP), a typical phthalic acid ester, is widespread in the environment and causes extensive concern due to its adverse effects on human health. To understand the genotoxicity of DMP at molecular level, the toxic interaction of DMP with herring sperm (hs) deoxyribonucleic acid (DNA; hs-DNA) was investigated in vitro under simulated physiological conditions using multi-spectroscopic techniques and a molecular modeling method. The results of Ultraviolet-Visible absorption spectroscopy, fluorescence emission spectroscopy, and circular dichroism spectra indicated that DMP interacts with hs-DNA in a groove-binding mode that changes the double helical structure of DNA. The binding constant and the number of binding sites calculated from the fluorescence quenching data were 565.718 L mol⁻¹ and 0.7872, respectively. A molecular modeling study revealed that DMP tends to bind with DNA in the A-T-rich regions of minor groove and that hydrogen bonding and van der Waals forces play main roles in the interaction. This research can help to elucidate the mechanism of DMP toxicity in vivo.

KEYWORDS:

• Multi-spectroscopic techniques
• molecular modeling
• dimethyl phthalate
• herring sperm DNA
• interaction mechanism

Funding

This work was supported by the Shandong Provincial Natural Science Foundation, China (ZR2014BQ033) and a China Postdoctoral Science Foundation funded project (2013M540297). The Natural Scientific Research Innovation Foundation in Harbin Institute of Technology (HIT; NSRIF.2014126) and the State Key Laboratory of Urban Water Resource and Environment HIT (2013DX09) are also acknowledged.