胆固醇-3-β, 5-α, 6-β-三醇通过活性氧的形成诱导遗传毒性。

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

作者信息

Cheng Y W, Kang J J, Shih Y L, Lo Y L, Wang C F

机构信息

School of Pharmacy, Taipei Medical University, No. 250, Wu-Shing Street, Taipei 101, Taiwan.

出版信息

Food Chem Toxicol. 2005 Apr;43(4):617-22. doi: 10.1016/j.fct.2005.01.007.

DOI:10.1016/j.fct.2005.01.007

PMID:15721210

Abstract

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.

摘要

本研究采用Ames试验和染色体畸变试验检测了氧化甾醇、胆固醇-3β,5α,6β-三醇（α-三醇）、7-酮胆固醇（7-酮）和胆固醇-5α,6α-环氧化物（α-环氧化物）的致突变性。仅α-三醇在缺乏代谢活化酶（S9）的情况下浓度依赖性地导致细菌回复突变体增加，而7-酮和α-环氧化物则不会。添加S9后，α-三醇的致突变作用减弱。另一方面，尽管α-三醇在有和没有S9的情况下均能显著诱导CHO-K1细胞发生染色体畸变。然而，与不添加S9混合液相比，添加S9降低了染色体异常结构的程度。过氧化氢酶和超氧化物歧化酶（SOD）抑制了α-三醇诱导的鼠伤寒沙门氏菌回复突变体增加以及CHO细胞染色体畸变频率，这表明活性氧（ROS）可能参与了α-三醇的遗传毒性作用。用α-三醇处理可增加CHO细胞中的ROS产生，而过氧化氢酶和SOD可使其减弱。本研究结果首次表明，α-三醇以ROS依赖的方式产生遗传毒性作用。