Characterization of the genotoxicity of anthraquinones in mammalian cells.
Naturally occurring 1,8-dihydroxyanthraquinones are under consideration as possible carcinogens. Here we wanted to elucidate a possible mechanism of their genotoxicity. All three tested anthraquinones, emodin, aloe-emodin, and danthron, showed capabilities to inhibit the non-covalent binding of bisbenzimide Hoechst 33342 to isolated DNA and in mouse lymphoma L5178Y cells comparable to the topoisomerase II inhibitor and intercalator m-amsacrine. In a cell-free decatenation assay, emodin exerted a stronger, danthron a similar and aloe-emodin a weaker inhibition of topoisomerase II activity than m-amsacrine. Analysis of the chromosomal extent of DNA damage induced by these anthraquinones was performed in mouse lymphoma L5178Y cells. Anthraquinone-induced mutant cell clones showed similar chromosomal lesions when compared to the topoisomerase II inhibitors etoposide and m-amsacrine, but were different from mutants induced by the DNA alkylator ethyl methanesulfonate. These data support the idea that inhibition of the catalytic activity of topoisomerase II contributes to anthraquinone-induced genotoxicity and mutagenicity.
Mueller
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Department of Toxicology, University of Würzburg, 97078, Würzburg, Germany. mueller1@niehs.nih.gov
Stopper
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D000504:Aloe / Q000737:chemistry; D000818:Animals; D000880:Anthraquinones / Q000633:toxicity*; D001562:Benzimidazoles; D004587:Electrophoresis, Agar Gel; D004642:Emodin / Q000031:analogs & derivatives / Q000633:toxicity; D005456:Fluorescent Dyes; D007940:Leukemia L5178; D015394:Molecular Structure; D009152:Mutagenicity Tests; D010946:Plants, Medicinal; D016133:Polymerase Chain Reaction / Q000379:methods; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured
D000880:Anthraquinones; D001562:Benzimidazoles; D005456:Fluorescent Dyes; D059005:Topoisomerase II Inhibitors; C518327:aloe emodin; D004642:Emodin; C017807:bisbenzimide ethoxide trihydrochloride; C004315:danthron