[Study, at the gene level, of the activation of topoisomerase II by antitumor agents].

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.