Cholesterol-3-beta, 5-alpha, 6-beta-triol induced genotoxicity through reactive oxygen species formation

The mutagenicity of oxysterols, cholesterol-3β,5α,6β-triol (α-Triol), 7-keto-cholesterol (7-Keto) and cholesterol-5α,6α- epoxide (α-Epox) were examined by the Ames method and chromosome aberration test in this study. Only α-Triol concentration-dependently caused an increase of bacterial revertants in the absence of metabolic activating enzymes (S9), but not 7-keto and α-Epox. The mutagenic effect of α-Triol was reduced by the addition of S9. On the other hand, although α-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 α-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 α-Triol. Treatment with α-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 α-Triol, causes genotoxic effect in an ROS-dependent manner.