PMID:6196777

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Citation

Mascharak, PK, Sugiura, Y, Kuwahara, J, Suzuki, T and Lippard, SJ (1983) Alteration and activation of sequence-specific cleavage of DNA by bleomycin in the presence of the antitumor drug cis-diamminedichloroplatinum(II). Proc. Natl. Acad. Sci. U.S.A. 80:6795-8

Abstract

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.

Links

PubMed PMC390072

Keywords

Animals; Base Sequence; Bleomycin/pharmacology; Cattle; Cisplatin/pharmacology; DNA/metabolism; DNA Restriction Enzymes; Kinetics; Thymus Gland

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