Assessing the mechanism of DNA damage induced by lead through direct and indirect interactions

Abstract

Lead still possesses great threats to human health owing to its widespread distribution in the environment caused by human activities, although various actions have been taken to cut down the use and distribution of lead. In this work, mechanisms of DNA damage caused by lead through indirect and direct interactions were investigated. Results from comet assay showed lead at 1–10μM induced DNA strand breaks in mice liver cells according to olive tail moment analysis. Signals of DNA–protein crosslinks (DPC) were not significantly detected until exposed at 100μM Pb2+. Further more, direct interactions between Pb2+ and DNA were explored to determine the binding mode between them using spectra analysis, isothermal titration calorimetry studies and molecular docking investigations, which indicated that Pb2+ could bind to DNA with four binding sites to form Pb2+–DNA complex by minor groove binding effects and electrostatic forces, resulting in damage to the structure of DNA double helix. Combined studies of lead genotoxicity in indirect (comet assay and DPC assay) and direct (binding mode investigations) interactions can be applied to study the potential damages to DNA induced by heavy metal pollutants.