TY - JOUR
T1 - Role of chromium(IV) in the chromium(VI)-related free radical formation, dG hydroxylation, and DNA damage
AU - Hai, Luo
AU - Lu, Yongde
AU - Yan, Mao
AU - Xianglin, Shi
AU - Dalal, Nar S.
PY - 1996/10
Y1 - 1996/10
N2 - 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.
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.
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U2 - 10.1016/0162-0134(95)00241-3
DO - 10.1016/0162-0134(95)00241-3
M3 - Article
C2 - 8837499
AN - SCOPUS:0030271894
SN - 0162-0134
VL - 64
SP - 25
EP - 35
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
IS - 1
ER -