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ToxSci Advance Access published online on March 14, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfj153
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received November 18, 2005
Accepted March 2, 2006

Genetic Toxicology

Mitochondrial and Nuclear DNA Damage Induced by Curcumin in Human Hepatoma G2 Cells

Jun Cao 1, Li Jia 2, Hui-Min Zhou 3, Yong Liu 4, and Lai-Fu Zhong 1 *

1 Department of Toxicology, Dalian Medical University, Dalian 116027, China
2 College of Laboratory Medicine, Dalian Medical University, Dalian 116027, China
3 Department of Microbiology, Dalian Medical University, Dalian 116027, China
4 Laboratory of Pharmaceutical Resource Discovery, Dalian Institute of Chemical Physics, the Chinese Academy of Sciences, Dalian 116023, China

* To whom correspondence should be addressed.
Lai-Fu Zhong, E-mail: rdrczhong{at}dlmedu.edu.cn


  Abstract

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 this natural compound possess both pro-and anti-oxidative effects. In this study, we found that curcumin induced DNA damage to both the mitochondrial and nuclear genomes in HepG2 cells. Using quantitative PCR 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 ROS 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.

Keywords: Curcumin; DNA damage; mitochondrial DNA; nuclear DNA; quantitative polymerase chain reaction; HepG2 cells.
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