Doxorubicin, DNA torsion, and chromatin dynamics

Intercalation of doxorubicin and formation of DNA adducts at active promoters increase torsional stress and enhance nucleosome turnover. Furthermore, doxorubicin traps topoisomerase II at breakage sites, which could further exacerbate torsional strain leading to higher nucleosome turnover in addition to causing double strand breaks. Enhanced nucleosome turnover might increase the exposure of naked DNA to DNA damaging agents such as reactive oxygen species (ROS) resulting in DNA damage and cell death.188