Characterization of the genotoxicity of anthraquinones in mammalian cells.

Abstract

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.

• Authors: S O Mueller, H Stopper
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1428 Issue 2-3 Pg. 406-14 (Aug 05 1999) ISSN: 0006-3002 [Print] Netherlands
• PMID: 10434060 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anthraquinones
• Benzimidazoles
• Fluorescent Dyes
• Topoisomerase II Inhibitors
• aloe emodin
• Emodin
• bisbenzimide ethoxide trihydrochloride
• danthron

Topics

• Aloe (chemistry)
• Animals
• Anthraquinones (toxicity)
• Benzimidazoles
• Electrophoresis, Agar Gel
• Emodin (analogs & derivatives, toxicity)
• Fluorescent Dyes
• Leukemia L5178
• Molecular Structure
• Mutagenicity Tests
• Plants, Medicinal
• Polymerase Chain Reaction (methods)
• Topoisomerase II Inhibitors
• Tumor Cells, Cultured