| Chromium(III)-Induced 8-Hydroxydeoxyguanosine in DNA and Its Reduction by Antioxidants: Comparative Effects of Melatonin, Ascorbate, and Vitamin E Wenbo Qi, Russel J. Reiter, Dun-Xian Tan, Joaquin J. Garcia, Lucien C. Manchester, Malgorzata Karbownik, and Juan R. Calvo Department of Cellular and Structural Biology, The University of Texas Health Science Center, San Antonio, Texas, USA Abstract
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 CrCl3 plus H2O2. We measured 8-OH-dG using HPLC with electrochemical detection. In the presence of H2O2, 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 µM 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. Key words: ascorbate, chromium, 8-hydroxydeoxyguanosine, melatonin, vitamin E. Environ Health Perspect 108:399-402 (2000) . [Online 16 March 2000] http://ehpnet1.niehs.nih.gov/docs/2000/108p399-402qi/ abstract.html Address correspondence to R.J. Reiter, Department of Cellular and Structural Biology, Mail Code 7762, The University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900 USA. Telephone: (210) 567-3859. Fax: (210) 567-6948. E-mail: reiter@uthscsa.edu This study was supported in part by the Amoun Pharmaceutical Industries Company. Received 27 August 1999 ; accepted 1 November 1999.
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