Alteration and activation of sequence-specific cleavage of DNA by bleomycin in the presence of the antitumor drug cis-diamminedichloroplatinum(II).
The antitumor drug cis-diamminedichloroplatinum(II) dramatically alters the sequence-specific cleavage of the bleomycin A2-iron(II)-O2 system. Preferred bleomycin cleavage sites adjacent to oligo(dG) regions on two restriction fragments of plasmid pBR322 DNA were masked by pretreatment with cis-diamminedichloroplatinum(II). trans-Diamminedichloroplatinum(II), which is inactive as an antitumor drug, showed similar but not identical behavior. The DNA-cleaving activity of bleomycin was substantially modified by cis-diamminedichloroplatinum(II), and a number of specific new cutting sites in guanine-rich parts of the sequence were activated by both isomers of the platinum complex. The results further emphasize the possibility that the synergism found when cis-diamminedichloroplatinum(II) and bleomycin are used in combination chemotherapy may be due to interactions at the level of DNA-drug binding.
D000818:Animals; D001483:Base Sequence; D001761:Bleomycin / Q000494:pharmacology*; D002417:Cattle; D002945:Cisplatin / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism*; D004262:DNA Restriction Enzymes; D007700:Kinetics; D013950:Thymus Gland
D001761:Bleomycin; D004247:DNA; D004262:DNA Restriction Enzymes; D002945:Cisplatin