Alteration and activation of sequence-specific cleavage of DNA by bleomycin in the presence of the antitumor drug cis-diamminedichloroplatinum(II).

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Abstract
The antitumor drug cis-diamminedichloroplatinum(II) (cis-DDP) dramatically alters the sequence-specific cleavage of the bleomyicn A2-Fe(II)-O2 system. Preferred bleomycin cleavage sites adjacent to oligo(dG) regions on 2 restriction fragments of plasmid pBR322 DNA were masked by pretreatment with cis-DDP. trans-DDP, which is inactive as an antitumor drug, showed similar but not identical behavior. The DNA-cleaving activity of bleomycin was substantially modified by cis-DDP and a number of specific new cutting sites in guanine-rich parts of the sequence were activated by both isomers of the Pt complex. The results further emphasize the possibility that the synergism found when cis-DDP and bleomycin are used in combination chemotherapy may be due to interactions at the level of DNA-drug binding.