[Effect of down-regulated hOGG1 gene expression on cytotoxicity and genotoxicity of hydroquinone].
OBJECTIVE
To explore the effects of down- regulated hOGG1 gene expression on cytotoxicity and genotoxicity of hydroquinone.


METHODS
A549 cells and A549-R cells with down- regulated hOGG1 gene were treated with different concentrations of hydroquinone (0, 5, 10, 20, 40 and 80 μmol/L). The cellular sensitivity and contents of ROS were measured by MTT assay and fluorescence method, respectively. The chromosome damage was measured by micronucleus test. The DNA damage and repair were examined using comet assay in both cells.


RESULTS
The cell viability decreased with increasing concentration of hydroquinone. The IC₅₀ of hydroquinone was 160.49 and 228.42 μmol/L in hOGG1 deficient A549-R cell and in A549 cell respectively (P < 0.05). When the dose of hydroquinone reached 5 micromol/L and above, the contents of ROS and the rate of micronucleated cells in A549-R cells were significantly higher than in A549 (P < 0.05) cells. At the same time, the comet rate and OTM in A549-R cells were significantly higher compared with A549 cells at 5 micromol/L and above in a dose-response way (P < 0.05). Furthermore, in DNA repair assay, A549-R cells with down- regulated hOGG1 gene were more difficult to repair than A549 cells. In A549-R cells, the comet rate and OTM reduced significantly until after 2 h repair time and even after 3 h the DNA damage was not repaired completely.


CONCLUSIONS
Oxidative damage may be one of the toxicological mechanisms of hydroquinone, and hOGG1 deficiency could increase sensitivity of A549-R cells to hydroquinone.
Department of Environmental, School of Public Health, Huaxi School of Public Health, Sichuan University, Chengdu 610041, China.
Ya
Y
Shu
Mei
M
Wu
Chen
C
Chen
Zun-zhen
ZZ
Zhang
D045744:Cell Line, Tumor; D002470:Cell Survival; D020552:Comet Assay; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics*; D015536:Down-Regulation; D006801:Humans; D006873:Hydroquinones / Q000633:toxicity*; D018384:Oxidative Stress
D006873:Hydroquinones; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; C031927:hydroquinone