Chromium(III)-induced 8-hydroxydeoxyguanosine in DNA and its reduction by antioxidants: comparative effects of melatonin, ascorbate, and vitamin E.
Chromium compounds are well documented carcinogens. Cr(III) is more reactive than Cr(VI) toward DNA under in vitro conditions. In the present study, we investigated the ability of Cr(III) to induce oxidative DNA damage by examining the formation of 8-hydroxydeoxyguanosine (8-OH-dG) in calf thymus DNA incubated with CrCl(3) plus H(2)O(2). We measured 8-OH-dG using HPLC with electrochemical detection. In the presence of H(2)O(2), we observed that Cr(III)-induced formation of 8-OH-dG in isolated DNA was dose and time dependent. Melatonin, ascorbate, and vitamin E (Trolox), all of which are free radical scavengers, markedly inhibited the formation of 8-OH-dG in a concentration-dependent manner. The concentration that reduced DNA damage by 50% was 0.51, 30.4, and 36.2 microM for melatonin, ascorbate, and Trolox, respectively. The results show that melatonin is 60- and 70-fold more effective than ascorbate or vitamin E, respectively, in reducing oxidative DNA damage in this in vitro model. These findings also are consistent with the conclusion that the carcinogenic mechanism of Cr(III) is possibly due to Cr(III)-mediated Fenton-type reactions and that melatonin's highly protective effects against Cr(III) relate, at least in part, to its direct hydroxyl radical scavenging ability.
Qi
W
W
Department of Cellular and Structural Biology, The University of Texas Health Science Center, San Antonio, Texas, USA.
Reiter
R J
RJ
Tan
D X
DX
Garcia
J J
JJ
Manchester
L C
LC
Karbownik
M
M
Calvo
J R
JR
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology; D002417:Cattle; D002857:Chromium / Q000633:toxicity*; D004247:DNA / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D066298:In Vitro Techniques; D008550:Melatonin / Q000494:pharmacology; D016273:Occupational Exposure; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D016166:Free Radical Scavengers; D002857:Chromium; D014810:Vitamin E; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D006861:Hydrogen Peroxide; D003849:Deoxyguanosine; D008550:Melatonin; D001205:Ascorbic Acid