Ethidium bromide changes the nuclease-sensitive DNA binding sites of the antitumor drug cis-diamminedichloroplatinum(II).
Exonuclease III has been shown previously to reveal the binding sites of the antitumor drug cis-diamminedichloroplatinum(II) on DNA. Pretreatment of the same DNA with the intercalator ethidium bromide causes new platinum binding sites to be detected by the exonuclease III method. In particular, a 5'd(G6-D-G2)3' sequence in a 165-base-pair restriction fragment of plasmid pBR322 becomes a preferred site for exonuclease III-detectable cis-diamminedichloroplatinum(II)binding. This switching of nuclease-sensitive platinum binding to new sites by the influence of another drug, ethidium bromide, offers an explantation at the molecular level for the phenomenon of synergism in combination chemotherapy.
D001483:Base Sequence; D002945:Cisplatin / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004357:Drug Synergism; D004996:Ethidium / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D013329:Structure-Activity Relationship
D004247:DNA; D004996:Ethidium; D002945:Cisplatin