Three Chemically Distinct Types of Oxidants Formed by Iron-Mediated Fenton Reactions in the Presence of DNA

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 91; no. 26; pp. 12438 - 12442
• Main Authors: Luo, Yongzhang, Han, Zhengxu, Chin, S. Michael, Linn, Stuart
• Format: Journal Article
• Language: English
• Published: United States National Academy of the Sciences of the United States of America 20.12.1994; National Acad Sciences; National Academy of Sciences
• Subjects: Bacteria; Biochemistry; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA Damage; DNA, Bacterial - chemistry; Dose response relationship; Dose-Response Relationship, Drug; Escherichia coli; Ethanol; Ethanol - chemistry; Ferrous Compounds - chemistry; Hydrogen Peroxide - chemistry; Ions; Iron; Iron - chemistry; Iron Chelating Agents - chemistry; Molecules; Mutagenesis; Oxidation-Reduction; Phosphates
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.26.12438

Exposure of Escherichia coli to H2O2leads to two kinetically distinguishable modes of killing: mode I killing occurs maximally near 2 mM H2O2, whereas mode II killing is essentially independent of H2O2concentrations up to 20 mM. A major portion of H2O2toxicity is attributed to DNA damage caused by the iron-mediated Fenton reaction. By studying DNA damage during Fenton reactions in vitro, the same complex kinetics were observed and three types of oxidants were distinguished based upon their reactivities toward H2O2and alcohols and upon iron-chelator effects. Type I oxidants are sensitive to H2O2but moderately resistant to ethanol; type II oxidants are resistant to both H2O2and ethanol; type III oxidants are sensitive to H2O2, ethanol, and t-butanol. To explain these results, we hypothesize that type I oxidants are generated upon Fe2+associated with DNA only through electrostatic interactions and cause mode I killing of E. coli; type II oxidants arise upon Fe2+, which is at least partially base-associated, and cause mode II killing; type III oxidants arise on Fe2+free in solution and probably do not cause killing. Therefore, particular interactions of DNA with transition metals should be considered to be an integral part of the chemistry and toxicity of H2O2.