Molecular insights into the interaction mechanism of endocrine-disrupting chemicals and DNA in laccase-induced polymerization transfer.

Abstract

Endocrine-disrupting chemicals (EDCs), such as 17β-estradiol (E2) and bisphenol A (BPA), can induce DNA damage, leading to genomic instability and cell death. Laccase, an enzyme secreted by diverse organisms, plays a critical role in mitigating the cytotoxicity of these contaminants. Despite its importance, the dynamic evolution and interaction mechanisms of EDCs and DNA in laccase catalysis remain poorly understood. This study investigates the interactions between EDCs and DNA during laccase-induced polymerization transfer at a molecular level. As the DNA concentration was increased from 0 to 7.575 nM, the pseudo-first-order kinetic constants for E2 and BPA decreased by 2.03 and 2.10 times, respectively. DNA-bound EDCs disrupted the catalytic activity and stability of laccase, thereby delaying the polymerization transfer rate of EDCs. E2 and BPA bound to DNA base pairs via groove and intercalative modes, respectively. Laccase-induced polymerization reduced damage to the DNA helix and base stacking caused by EDC binding. Moreover, the resulting DNA-EDC-precipitated polymers, formed through continuous laccase polymerization, exhibited denser and more complex structures compared with spherical EDC-precipitated polymers, confirming DNA encapsulation and/or binding. This work underscores the intramolecular mechanisms of EDC interaction with DNA in vitro during the laccase-induced polymerization, offering efficient ways to mitigate the genotoxicity of EDCs.