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  • Title: [Study, at the gene level, of the activation of topoisomerase II by antitumor agents].
    Author: Vilarem MJ, Riou JF, Riou G, Larsen CJ.
    Journal: Pathol Biol (Paris); 1987 Nov; 35(9):1263-9. PubMed ID: 2827094.
    Abstract:
    Most experimental data clearly suggest that antitumor agents including DNA intercalative molecules (acridine derivatives, ellipticine and derivatives), or non intercalative ones (epipodophyllotoxines), exert their cytotoxic activity by stabilizing DNA-Topoisomerase II complexes. This phenomenon can be revealed by the presence of DNA breaks upon protein denaturing treatment. In this work, BD-40, an ellipticine analog has been shown to interact in vivo with Topoisomerase II. Moreover, cleavage sites generated by the drug treatment in human proto-oncogene c-myc appear to be mostly localized in the 5' end of the gene locus, which contains regulatory elements. Some of these sites are in a striking correspondence with DNAse I hypersensitive sites, which reportedly reflect the state of activity of genes.
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