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Reevaluation of interaction of cis-dichloro(ethylenediamine)platinum(II) with DNA

Journal Article · · Biochemistry; (United States)
DOI:https://doi.org/10.1021/bi00361a026· OSTI ID:6868284
Intrastrand cross-links represent the majority of modifications in DNA resulting from interaction with the cancer chemotherapeutic drug cis-diamminedichloroplatinum(II) (cis-DDP). These adducts were recently characterized although several discrepancies remained to be resolved. In these studies, (/sup 3/H)-cis-dichloro(ethylenediamine)platinum(II) (cis-DEP) was used because of the convenience of the radiolabel; this analogue produces adducts at identical sites in DNA at cis-DDP. The adduct at AG sequences invariably has adenine on the 5'-terminus of the dimer. After short incubations, with cis-DEP and removal of unreacted drug, the monofunctional adducts slowly rearranged to bifunctional adducts. It is suggested that this evolution of adducts may result from the drug walking along the double helix, a phenomenon that does not appear to occur in single-stranded DNA.
Research Organization:
Univ. of Nebraska Medical Center, Omaha (USA)
OSTI ID:
6868284
Journal Information:
Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 25:13; ISSN BICHA
Country of Publication:
United States
Language:
English