In vivo and in vitro stimulation by antitumor drugs of the topoisomerase II-induced cleavage sites in c-myc proto-oncogene.
Stimulation of topoisomerase II cleavage activity by antitumor drugs with or without DNA intercalative ability has been tested in vivo on the c-myc proto-oncogene. Two human tumor cell lines (N417 and HL60 cells) were treated with mAMSA, OH-9-ellipticine, VM26, and BD-40 (an aza-ellipticine analog), and DNA breaks were mapped in the gene locus by Southern blot hybridization with c-myc probes. Most of the major cleavage sites induced in vivo by drugs in the 5' end of c-myc were also observed in vitro using purified topoisomerase II and a c-myc gene DNA insert. Moreover, they closely mapped to some DNAse I hypersensitive sites, the presence of which reflects gene activity. DNA from drug treated cells probed with a human beta 1 globin pseudogene, and the c-mos proto-oncogene did not reveal topoisomerase II cleavage bands, suggesting that topoisomerase II-mediated drug activity may correlate with gene activity.
Riou
J F
JF
Vilarem
M J
MJ
Larsen
C J
CJ
Multon
E
E
Riou
G F
GF
D000677:Amsacrine / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002460:Cell Line; D004262:DNA Restriction Enzymes; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000187:drug effects / Q000235:genetics; D006801:Humans; D009710:Nucleotide Mapping; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes / Q000187:drug effects; D013713:Teniposide / Q000494:pharmacology
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D000677:Amsacrine; D013713:Teniposide; D004262:DNA Restriction Enzymes; D004250:DNA Topoisomerases, Type II