Genotoxic effect of 6-gingerol on human hepatoma G2 cells.
6-gingerol, a major component of ginger, has antioxidant, anti-apoptotic, and anti-inflammatory activities. However, some dietary phytochemicals possess pro-oxidant effects as well, and the risk of adverse effects is increased by raising the use of doses. The aim of this study was to assess the genotoxic effects of 6-gingerol and to clarify the mechanisms, using human hepatoma G2 (HepG2) cells. Exposure of the cells to 6-gingerol caused significant increase of DNA migration in comet assay, increase of micronuclei frequencies at high concentrations at 20-80 and 20-40 microM, respectively. These results indicate that 6-gingerol caused DNA strand breaks and chromosome damage. To further elucidate the underlying mechanisms, we tested lysosomal membrane stability, mitochondrial membrane potential, the intracellular generation of reactive oxygen species (ROS) and reduced glutathione (GSH). In addition, the level of oxidative DNA damage was evaluated by immunocytochemical analysis on 8-hydroxydeoxyguanosine (8-OHdG). Results showed that lysosomal membrane stability was reduced after treatment by 6-gingerol (20-80 microM) for 40 min, mitochondrial membrane potential decreased after treatment for 50 min, GSH and ROS levels were significantly increased after treatment for 60 min. These suggest 6-gingerol induces genotoxicity probably by oxidative stress; lysosomal and mitochondrial damage were observed in 6-gingerol-induced toxicity.
Yang
Guang
G
Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, China.
Zhong
Laifu
L
Jiang
Liping
L
Geng
Chengyan
C
Cao
Jun
J
Sun
Xiance
X
Ma
Yufang
Y
D000080242:8-Hydroxy-2'-Deoxyguanosine; D006528:Carcinoma, Hepatocellular / Q000235:genetics; D002396:Catechols / Q000009:adverse effects*; D049109:Cell Proliferation / Q000187:drug effects; D053960:DNA Breaks / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005233:Fatty Alcohols / Q000009:adverse effects*; D005978:Glutathione / Q000378:metabolism; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects; D008247:Lysosomes / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009153:Mutagens / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D002396:Catechols; D005233:Fatty Alcohols; D009153:Mutagens; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; C007845:gingerol; D003849:Deoxyguanosine; D005978:Glutathione