ToxSci Advance Access originally published online on March 14, 2006
Toxicological Sciences 2006 91(2):476-483; doi:10.1093/toxsci/kfj153
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Mitochondrial and Nuclear DNA Damage Induced by Curcumin in Human Hepatoma G2 Cells
* Department of Toxicology, College of Laboratory Medicine, and Department of Microbiology, Dalian Medical University, Dalian 116027, China; and Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, the Chinese Academy of Sciences, Dalian 116023, China
Received November 18, 2005; accepted March 2, 2006
Curcumin is extensively used as a spice and pigment and has anticarcinogenic effects that could be linked to its antioxidant properties. However, some studies suggest that this natural compound possesses both pro- and antioxidative effects. In this study, we found that curcumin induced DNA damage to both the mitochondrial and nuclear genomes in human hepatoma G2 cells. Using quantitative polymerase chain reaction and immunocytochemistry staining of 8-hydroxydeoxyguanosine, we demonstrated that curcumin induced dose-dependent damage in both the mitochondrial and nuclear genomes and that the mitochondrial damage was more extensive. Nuclear DNA fragments were also evident in comet assays. The mechanism underlies the elevated level of reactive oxygen species and lipid peroxidation generated by curcumin. The lack of DNA damage at low doses suggested that low levels of curcumin does not induce DNA damage and may play an antioxidant role in carcinogenesis. But at high doses, we found that curcumin imposed oxidative stress and damaged DNA. These data reinforce the hypothesis that curcumin plays a conflicting dual role in carcinogenesis. Also, the extensive mitochondrial DNA damage might be an initial event triggering curcumin-induced cell death.
Key Words: curcumin; DNA damage; mitochondrial DNA; nuclear DNA; quantitative polymerase chain reaction; HepG2 cells.
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