Cholesterol-3-beta, 5-alpha, 6-beta-triol induced genotoxicity through reactive oxygen species formation.
The mutagenicity of oxysterols, cholesterol-3beta,5alpha,6beta-triol (alpha-Triol), 7-keto-cholesterol (7-Keto) and cholesterol-5alpha,6alpha-epoxide (alpha-Epox) were examined by the Ames method and chromosome aberration test in this study. Only alpha-Triol concentration-dependently caused an increase of bacterial revertants in the absence of metabolic activating enzymes (S9), but not 7-keto and alpha-Epox. The mutagenic effect of alpha-Triol was reduced by the addition of S9. On the other hand, although alpha-Triol significantly induced chromosome aberration in CHO-K1 cells with and without S9. However, the addition of S9 reduced the degree of abnormal structure chromosome compared to without S9 mix. Catalase and superoxide dismutase (SOD) inhibited alpha-Triol induced increase of revertants in Salmonella typhimurium and chromosome aberration frequency in CHO cells, suggesting that reactive oxygen species (ROS) might be involved in the genotoxic effect of alpha-Triol. Treatment with alpha-Triol increased the ROS production in CHO cells, which could be attenuated by catalase and SOD. Results in this study suggested, for the first time that alpha-Triol, causes genotoxic effect in an ROS-dependent manner.
Cheng
Y W
YW
School of Pharmacy, Taipei Medical University, No. 250, Wu-Shing Street, Taipei 101, Taiwan. ywcheng@tmu.edu.tw
Kang
J J
JJ
Shih
Y L
YL
Lo
Y L
YL
Wang
C F
CF
D000818:Animals; D016466:CHO Cells; D002374:Catalase / Q000494:pharmacology; D002777:Cholestanols / Q000633:toxicity*; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000633:toxicity*; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D007653:Ketocholesterols / Q000633:toxicity*; D009152:Mutagenicity Tests; D017382:Reactive Oxygen Species; D012475:Salmonella / Q000235:genetics; D013482:Superoxide Dismutase / Q000494:pharmacology
D002777:Cholestanols; D007653:Ketocholesterols; D017382:Reactive Oxygen Species; C000474:cholestane-3,5,6-triol; C002415:cholesterol alpha-oxide; D002784:Cholesterol; D002374:Catalase; D013482:Superoxide Dismutase; C003001:7-ketocholesterol