Genotoxicity of etoposide: greater susceptibility of MLL than other target genes.
The ability of topoisomerase 2 inhibitors to induce DNA breakage is well recognized. Previous studies, however, have concentrated on the effects on individual genes. The effects of etoposide on the MLL, RUNX1, and MLLT3 genes were simultaneously studied in the same hemopoietic cell population. We found MLL to be more susceptible to etoposide-induced cleavage than RUNX1 and MLLT3, with maximum cleavage at a lower drug concentration. A higher level of MLL than other gene cleavage was also detected after cellular exposure to all drug concentrations. Greater susceptibility to topoisomerase 2 inhibitor-induced cleavage may explain the more frequent involvement of MLL in treatment-related leukemogenesis.
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Immunogenetics Laboratory, University of Manchester, Oxford Road, Manchester, UK M13 3PL. antng@blueyonder.co.uk
Taylor
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D050676:Core Binding Factor Alpha 2 Subunit / Q000187:drug effects / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000633:toxicity; D005047:Etoposide / Q000494:pharmacology / Q000633:toxicity*; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics / Q000473:pathology; D009152:Mutagenicity Tests; D051788:Myeloid-Lymphoid Leukemia Protein / Q000187:drug effects* / Q000235:genetics*; D009687:Nuclear Proteins / Q000187:drug effects / Q000235:genetics; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured
D050676:Core Binding Factor Alpha 2 Subunit; D004791:Enzyme Inhibitors; C489901:MLLT3 protein, human; D009687:Nuclear Proteins; C493728:RUNX1 protein, human; D059005:Topoisomerase II Inhibitors; D051788:Myeloid-Lymphoid Leukemia Protein; D005047:Etoposide