[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.
Vilarem
M J
MJ
U-301 INSERM, Hôpital, Saint-Louis, Paris, France.
Riou
J F
JF
Riou
G
G
Larsen
C J
CJ
D000470:Alkaloids / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004261:DNA Replication; D004250:DNA Topoisomerases, Type II / Q000235:genetics*; D004611:Ellipticines / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D007364:Intercalating Agents / Q000494:pharmacology*; D007546:Isoquinolines; D009857:Oncogenes / Q000187:drug effects; D000090063:Proto-Oncogene Mas; D014158:Transcription, Genetic
D000470:Alkaloids; D000970:Antineoplastic Agents; D004611:Ellipticines; D007211:Indoles; D007364:Intercalating Agents; D007546:Isoquinolines; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C024256:pazelliptine; D004250:DNA Topoisomerases, Type II
Etude au niveau génique de l'activation de la topoisomerase II par des agents antitumoraux.