Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Genotoxicity of the laxative drug components emodin, aloe-emodin and danthron in mammalian cells: topoisomerase II mediated? 900 18

We had reported that the plant-derived 1,8-dihydroxyanthraquinone derivatives, emodin and danthron, were clearly genotoxic in mouse lymphoma L5178Y cells, whereas chrysophanol was only weakly genotoxic and physcion not at all. Danthron was more potent than emodin. Furthermore, we had found that these compounds bound non-covalently to DNA and inhibited topoisomerase II activity. Interestingly, in these systems emodin was more potent than danthron. This inversion of the ranking prompted us to investigate the underlying mechanism. Since emodin shows a high serum-protein binding affinity, horse serum used as a media-supplement in the mouse lymphoma genotoxicity assays was analyzed for a potential selective scavenging of emodin. Non-covalent DNA-binding in mouse lymphoma L5178Y cells was investigated in the absence or presence of serum. In the presence of 10% serum, the DNA-binding potency of emodin was markedly reduced and was lower than that of danthron. We also applied mutation assays with mouse lymphoma cells and AS52 cells and varied the serum concentration used. In the absence of serum emodin showed slightly higher mutagenicity in AS52 cells than danthron. At reduced serum concentration (0.5%) emodin was strongly cytotoxic to the mouse lymphoma cells. For chrysophanol and physcion, a considerable reduction of the non-covalent DNA-binding potency in intact cells was found when compared to danthron, in concordance with their lower genotoxic potency. Overall, these data support the understanding that the genotoxicity of anthraquinones is, at least in part, mediated by non-covalent DNA-binding.
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PMID:Factors affecting the genotoxic potency ranking of natural anthraquinones in mammalian cell culture systems. 963 May 66