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. 1982 Jun;79(11):3489-92.
doi: 10.1073/pnas.79.11.3489.

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

T D Tullius, S J Lippard

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

T D Tullius et al. Proc Natl Acad Sci U S A. 1982 Jun.

Abstract

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.

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