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 t heir genotoxicity. All three tested anthraquinones, emodin, aloe-emodin, an d danthron, showed capabilities to inhibit the non-covalent binding of bisb enzimide Hoechst 33342 to isolated DNA and in mouse lymphoma L5178Y cells c omparable to the topoisomerase II inhibitor and intercalator m-amsacrine. I n a cell-free decatenation assay, emodin exerted a stronger, danthron a sim ilar and aloe-emodin a weaker inhibition of topoisomerase II activity than m-amsacrine. Analysis of the chromosomal extent of DNA damage induced by th ese anthraquinones was performed in mouse lymphoma L5178Y cells. Anthraquin one-induced mutant cell clones showed similar chromosomal lesions when comp ared 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 muta genicity. (C) 1999 Elsevier Science B.V. All rights reserved.