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抱子甘蓝对苯并[a]芘诱导的DNA损伤的保护作用:单细胞凝胶电泳(SCGE)/Hep G2检测法的模型研究

Protective effects of Brussels sprouts towards B[a]P-induced DNA damage: a model study with the single-cell gel electrophoresis (SCGE)/Hep G2 assay.

作者信息

Laky B, Knasmüller S, Gminski R, Mersch-Sundermann V, Scharf G, Verkerk R, Freywald C, Uhl M, Kassie F

机构信息

Insitute of Cancer Research, University of Vienna, Borschkegasse 8A, 1090 Vienna, Austria.

出版信息

Food Chem Toxicol. 2002 Aug;40(8):1077-83. doi: 10.1016/s0278-6915(02)00031-5.

DOI:10.1016/s0278-6915(02)00031-5
PMID:12067567
Abstract

The aim of this study was to investigate the chemoprotective effects of Brussels sprouts juice towards benzo[a]pyrene (B(a)P)-induced DNA damage in the single-cell gel electrophoresis (SCGE)/Hep G2 test system. This assay combines the advantages of the SCGE assay with that of the use of human-derived cells possessing inducible phase I and phase II enzymes. Co-treatment of Hep G2 cells with small amounts of Brussels sprouts juice (0.25-2.0 microl/ml) and B(a)P reduced the genotoxic effect of the latter in a dose-dependent manner. Contrary to the results with the crude juice, unexpected synergistic effects were observed with allyl isothiocyanate (AITC, 1.0-6.0 microM), a breakdown product of sinigrin, which is the most abundant glucosinolate in Brussels sprouts. Although these concentrations of AITC did not cause DNA damage per se, at higher concentrations (> or =25 microM), the compound caused a pronounced dose-dependent DNA damage by itself. Mechanistic studies showed that Brussels sprouts juice causes induction of activities of ethoxyresorufin O-deethylase (EROD) and glutathione S-transferase (GST) at dose levels which were protective towards B(a)P. In combined treatment experiments with (+/-)-anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE, 5.0 microM), the main genotoxic metabolite of B(a)P, and Brussels sprouts juice, only weak protection was found indicating that the mechanism of chemoprotection of Brussels sprouts is not mediated through inactivation of this metabolite. In conclusion, our findings show that Brussels sprouts are highly protective against B(a)P-induced DNA damage in human-derived cells.

摘要

本研究旨在调查抱子甘蓝汁对苯并[a]芘(B(a)P)在单细胞凝胶电泳(SCGE)/Hep G2测试系统中诱导的DNA损伤的化学保护作用。该检测方法结合了SCGE检测方法的优点以及使用具有诱导性I相和II相酶的人源细胞的优点。用少量抱子甘蓝汁(0.25 - 2.0微升/毫升)与B(a)P共同处理Hep G2细胞,可呈剂量依赖性降低后者的遗传毒性作用。与粗汁的结果相反,异硫氰酸烯丙酯(AITC,1.0 - 6.0微摩尔)观察到意外的协同效应,AITC是黑芥子硫苷酸钾的分解产物,而黑芥子硫苷酸钾是抱子甘蓝中含量最丰富的硫代葡萄糖苷。尽管这些浓度的AITC本身不会导致DNA损伤,但在较高浓度(≥25微摩尔)时,该化合物自身会导致明显的剂量依赖性DNA损伤。机制研究表明,抱子甘蓝汁在对B(a)P具有保护作用的剂量水平下会导致乙氧基异吩恶唑酮O - 脱乙基酶(EROD)和谷胱甘肽S - 转移酶(GST)活性的诱导。在用(±) - 反式 - 苯并[a]芘 - 7,8 - 二氢二醇 - 9,10 - 环氧化物(BPDE,5.0微摩尔)(B(a)P的主要遗传毒性代谢物)和抱子甘蓝汁进行的联合处理实验中,仅发现微弱的保护作用,这表明抱子甘蓝的化学保护机制不是通过该代谢物的失活介导。总之,我们的研究结果表明,抱子甘蓝对人源细胞中B(a)P诱导的DNA损伤具有高度保护作用。

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