GENOTOXICITY OF THE LAXATIVE DRUG COMPONENTS EMODIN, ALOE-EMODIN AND DANTHRON IN MAMMALIAN-CELLS - TOPOISOMERASE-II MEDIATED

1,8-Dihydroxyanthraquinones are under debate as plant-derived carcinog ens 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 rk-mutations in mouse lymph oma L5178Y cells. Induction of micronuclei also occurred in the same c ell line, and was dose-dependent, with the potency ranking being danth ron > aloe-emodin > emodin. In a DNA decatenation assay with a network of mitochondrial DNA of C. fasciulata, all three test compounds inhib ited the topoisomerase II-mediated decatenation, Danthron and aloe-emo din, but not emodin, increased the fraction of DNA moving into comet t ails when tested at concentrations around 50 mu M in single-cell gel-e lectrophoresis 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 top oisomerase II inhibitor. All three test chemicals were effective in th is pretreatment protocol, with danthron again being the most potent. G iven clearcut evidence of their genotoxic activity, further research o n the human cancer risk of these compounds may be warranted.