Chromium (Cr) compounds are widely used industrial chemicals and well known
carcinogens. Cr(III) was earlier found to induce oxidative damage as documented by examining the levels of
8-hydroxydeoxyguanosine (8-OH-dG), an index for DNA damage, in isolated
calf thymus DNA incubated with CrCl(3) and H(2)O(2). In the present in vitro study, we compared the ability of the
free radical scavengers melatonin, N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (
AFMK),
resveratrol and
uric acid to reduce DNA damage induced by Cr(III). Each of these scavengers markedly reduced the DNA damage in a concentration-dependent manner. The concentrations that reduced
8-OH-dG formation by 50% (IC(50)) were 0.10 microM for both
resveratrol and
melatonin, and 0.27 microM for
AFMK. However, the efficacy of the fourth
endogenous antioxidant, i.e.
uric acid, in terms of its inhibition of DNA damage in the same in vitro system was about 60--150 times less effective than the other scavengers; the IC(50) for
uric acid was 15.24 microM. These findings suggest that three of the four
antioxidants tested in these studies may have utility in protecting against the
environmental pollutant Cr and that the protective effects of these
free radical scavengers against Cr(III)-induced
carcinogenesis may relate to their direct
hydroxyl radical scavenging ability. In the present study, the formation of
8-OH-dG was likely due to a Cr(III)-mediated Fenton-type reaction that generates
hydroxyl radicals, which in turn damage
DNA. Once formed,
8-OH-dG can mutate eventually leading to
cancer; thus the implication is that these
antioxidants may reduce the incidence of Cr-related
cancers.