Importance of Locations of Iron Ions to Elicit Cytotoxicity Induced by a Fenton-Type Reaction

Kintaro Igarashi, Yoshimi Shoji, Emiko Sekine-Suzuki, Megumi Ueno, Ken Ichiro Matsumoto, Ikuo Nakanishi, Koji Fukui

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


The impact of the site of the Fenton reaction, i.e., hydroxyl radical (OH) generation, on cytotoxicity was investigated by estimating cell lethality in rat thymocytes. Cells were incubated with ferrous sulfate (FeSO4) and hydrogen peroxide (H2O2), or pre-incubated with FeSO4 and then H2O2 was added after medium was replaced to remove iron ions or after the medium was not replaced. Cell lethality in rat thymocytes was estimated by measuring cell sizes using flow cytometry. High extracellular concentrations of FeSO4 exerted protective effects against H2O2-induced cell death instead of enhancing cell lethality. The pre-incubation of cells with FeSO4 enhanced cell lethality induced by H2O2, whereas a pre-incubation with a high concentration of FeSO4 exerted protective effects. FeSO4 distributed extracellularly or on the surface of cells neutralized H2O2 outside cells. Cytotoxicity was only enhanced when the Fenton reaction, i.e., the generation of OH, occurred inside cells. An assessment of plasmid DNA breakage showed that OH induced by the Fenton reaction system did not break DNA. Therefore, the main target of intracellularly generated OH does not appear to be DNA.

Original languageEnglish
Article number3642
Issue number15
Publication statusPublished - 2022 Aug


  • Fenton reaction
  • cytotoxicity
  • hydrogen peroxide
  • hydroxyl radical
  • iron ion
  • molecular distribution
  • oxidative stress
  • plasmid DNA
  • rat thymocyte
  • reactive oxygen species

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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