Chromium (IV)-mediated Fenton-like reaction causes DNA damage: Implication to genotoxicity of chromate

This paper describes our deoxyribonucleic acid (DNA) damage and Fenton activity studies on Cr(IV) that were undertaken to examine a role of Cr(IV) in the biochemical mechanism of genotoxicity of Cr(VI) compounds. A Cr(IV)- containing compound, a Cr(IV)-ester, was synthesized and used as the first model compound for Cr(IV) studies. Electron spin resonance measurements demonstrated that in the presence of H₂O₂, this Cr(IV) compound acts as a potent Fenton-like reagent, i.e., it generates ·OH radical and a Cr(V) species (g = 1.9787) via: Cr(IV) + H₂O₂ → Cr(V) + ·OH + OH^-. Measurements of ·OH yield as a function of H₂O₂ concentration showed that Cr(IV) is more potent than Cr(V) in generating ·OH. DNA damage assays demonstrate that Cr(IV) and the Cr(IV)/H₂O₂-generated ·OH radical can cause DNA strand breaks. The DNA damage caused by ·OH radical can be effectively blocked by ·OH radical scavengers. These results thus constitute the first direct evidence for DNA damage by Cr(IV) and Cr(IV)-mediated Fenton-like reaction and support the conjecture that Cr(IV) plays a significant role in the biochemical mechanism of the genotoxic reactions of Cr(VI) compounds and that this effect can be modulated by suitable antiradical agents.