Role of chromium(IV) in the chromium(VI)-related free radical formation, dG hydroxylation, and DNA damage

Luo Hai, Yongde Lu, Mao Yan, Shi Xianglin, Nar S. Dalal

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


A reactive Cr(IV) ester was synthesized from a reaction of CrO3 with 2,4-dimethyl-2,4-pentanediol as verified by electron spin resonance (ESR) and magnetic susceptibility measurements. ESR spin trapping studies demonstrate that the Cr(IV) ester is capable of generating hydroxyl free radical (·OH) through a Fenton-like mechanism (Cr(IV) + H2O2 → Cr(V) + ·OH + OH-) with a concomitant generation of Cr(V) species (g = 1.9787). Cr(IV) caused DNA strand breaks as measured by electrophoretic assays. H2O2 enhanced the DNA strand breaks via ·OH formation by a Cr(IV)-mediated Fenton-like reaction. In the Cr(IV)/H2O2 system, formate did not block Cr(V) formation, but prevented DNA damage, indicating that ·OH radicals, and not Cr(V), caused the DNA damage. Reaction of Cr(VI) with ascorbate was also used as a source of Cr(IV). Incubation of Cr(VI), ascorbate, and DNA caused DNA strand breaks. A free radical trap, 5,5-dimethyl-1-pyrroline (DMPO), only slightly inhibited the DNA damage. Addition of Mn(II), which inhibited Cr(IV), caused significant protection. H2O2 enhanced the DNA damage via Cr(IV)-mediated ·OH radical generation and Mn(II) inhibited the damage, again showing that Cr(IV) and its related ·OH generation caused DNA strand breaks. HPLC measurements showed that ·OH radicals generated by a Cr(IV)-mediated Fenton- like reaction generated 8-hydroxy-2'-deoxyguanosine from 2'-deoxyguanosine. The results demonstrate that Cr(IV) and its generated ·OH radicals are capable of damaging DNA. Moreover, in comparison with Cr(V), Cr(IV) is a more potent DNA damaging agent.

Original languageEnglish
Pages (from-to)25-35
Number of pages11
JournalJournal of Inorganic Biochemistry
Issue number1
StatePublished - Oct 1996

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry


Dive into the research topics of 'Role of chromium(IV) in the chromium(VI)-related free radical formation, dG hydroxylation, and DNA damage'. Together they form a unique fingerprint.

Cite this