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.