Hydrogen peroxide and iron ions can modulate lipid peroxidation, apoptosis, and the cell cycle, but do not have a significant effect on DNA double-strand break

Hydroxyl radical (·OH) generated by the Fenton reaction between transition metal ions and hydrogen peroxide (H2O2) can induce significant cellular damage. However, the specific mechanism of ·OH-induced cell death has not been systematically studied. In this study, we reacted FeSO4 and Fe3O4 magnetic nanoparticles with H2O2 and found that ·OH generated from the intracellular Fenton reaction can lead to significant cell death. The Fenton reaction between Fe2+ with H2O2 resulted in a shift in lipid peroxidation and cell cycle arrest. It is noteworthy that the ·OH generated from the Fenton reaction triggered severe apoptosis but did not lead to DNA double-strand breakage. Our results suggest that the Fenton reaction had acute cytotoxicity, which was primarily due to ·OH produced from the Fenton reaction inducing lipid peroxidation and apoptosis and modulating the cell cycle, but not by inducing DNA damage.