Ethidium bromide changes the nuclease-sensitive DNA binding sites of the antitumor drug cis-diamminedichloroplatinum(II).

Abstract

Exonuclease III reveals the binding sites of the antitumor drug cis-diamminedichloroplatinum(II) on DNA. Pretreatment of the same DNA with the intercalator ethidium bromide causes new Pt binding sites to be detected by the exonuclease III method. In particular, a 5''d(G6-C-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 Pt binding to new sites by the influence of another drug, ethidium bromide, offers an explanation at the molecular level for the phenomenon of synergism in combination chemotherapy.