PMID- 8837499 OWN - NLM STAT- MEDLINE DCOM- 19961211 LR - 20190909 IS - 0162-0134 (Print) IS - 0162-0134 (Linking) VI - 64 IP - 1 DP - 1996 Oct TI - Role of chromium(IV) in the chromium(VI)-related free radical formation, dG hydroxylation, and DNA damage. PG - 25-35 AB - 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. FAU - Luo, H AU - Luo H AD - Department of Chemistry, West Virginia University, Morgantown 26506, USA. FAU - Lu, Y AU - Lu Y FAU - Mao, Y AU - Mao Y FAU - Shi, X AU - Shi X FAU - Dalal, N S AU - Dalal NS LA - eng PT - Journal Article PL - United States TA - J Inorg Biochem JT - Journal of inorganic biochemistry JID - 7905788 RN - 0 (Free Radicals) RN - 0R0008Q3JB (Chromium) RN - 9007-49-2 (DNA) RN - G9481N71RO (Deoxyguanosine) SB - IM MH - Chromium/chemistry/*toxicity MH - DNA/chemistry/drug effects MH - *DNA Damage MH - Deoxyguanosine/chemistry MH - Electron Spin Resonance Spectroscopy MH - Free Radicals/chemistry/toxicity MH - Hydroxylation EDAT- 1996/10/01 00:00 MHDA- 1996/10/01 00:01 CRDT- 1996/10/01 00:00 PHST- 1996/10/01 00:00 [pubmed] PHST- 1996/10/01 00:01 [medline] PHST- 1996/10/01 00:00 [entrez] AID - 0162-0134(95)00241-3 [pii] AID - 10.1016/0162-0134(95)00241-3 [doi] PST - ppublish SO - J Inorg Biochem. 1996 Oct;64(1):25-35. doi: 10.1016/0162-0134(95)00241-3.