Müller S O, Eckert I, Lutz W K, Stopper H
Department of Toxicology, University of Würzburg, Germany.
Mutat Res. 1996 Dec 20;371(3-4):165-73. doi: 10.1016/s0165-1218(96)90105-6.
1,8-Dihydroxyanthraquinones are under debate as plant-derived carcinogens that are found in laxatives, food colors, and possibly vegetables. Published genotoxicity data are controversial, and so three of them (emodin, danthron and aloe-emodin) were tested in a number of in vitro assay systems. All three compounds induced tk-mutations in mouse lymphoma L5178Y cells. Induction of micronuclei also occurred in the same cell line, and was dose-dependent, with the potency ranking being danthron > aloe-emodin > emodin. In a DNA decatenation assay with a network of mitochondrial DNA of C. fasciulata, all three test compounds inhibited the topoisomerase II-mediated decatenation. Danthron and aloe-emodin, but not emodin, increased the fraction of DNA moving into comet tails when tested at concentrations around 50 microM in single-cell gel-electrophoresis assays (SCGE; comet assay). Comet assays were also used in modified form to determine whether pretreatment of the cells with the test compounds would reduce the effects of etoposide, a potent topoisomerase II inhibitor. All three test chemicals were effective in this pretreatment protocol, with danthron again being the most potent. Given clearcut evidence of their genotoxic activity, further research on the human cancer risk of these compounds may be warranted.
1,8 - 二羟基蒽醌作为一种植物源性致癌物存在争议，它存在于泻药、食用色素以及可能的蔬菜中。已发表的遗传毒性数据存在争议，因此对其中三种（大黄素、丹蒽醌和芦荟大黄素）在多种体外检测系统中进行了测试。这三种化合物均在小鼠淋巴瘤L5178Y细胞中诱导了tk基因突变。在同一细胞系中也出现了微核诱导现象，且呈剂量依赖性，效力排序为丹蒽醌>芦荟大黄素>大黄素。在一项使用fasciulata线粒体DNA网络的DNA解连环测定中，所有三种受试化合物均抑制了拓扑异构酶II介导的解连环作用。在单细胞凝胶电泳测定（SCGE；彗星试验）中，当以约50微摩尔的浓度进行测试时，丹蒽醌和芦荟大黄素（而非大黄素）增加了进入彗星尾的DNA比例。彗星试验也以改良形式用于确定用受试化合物对细胞进行预处理是否会降低依托泊苷（一种有效的拓扑异构酶II抑制剂）的作用。在这种预处理方案中，所有三种受试化学物质均有效，丹蒽醌再次最为有效。鉴于有明确证据表明它们具有遗传毒性活性，可能有必要对这些化合物对人类癌症风险进行进一步研究。
