title: DNA sequence selectivity of cisplatin analogues in intact human cells.
abstract: The sequence specificity of ten cisplatin analogues was examined in intact human cells. Six of these compounds have anti-tumour activity. The sequence selectivity was investigated using a Taq DNA polymerase/linear amplification assay on damaged DNA extracted from treated cells. Cisplatin and tetraplatin(IV) produced strong damage and DACH RR(II) and cis-[Pt(II)Cl,2(iPrNH2)2] weak DNA damage in intact HeLa cells. The sequence selectivity of tetraplatin(IV) in intact human cells was very similar to that of cisplatin and favored runs of consecutive purines, especially consecutive guanines. The compounds transplatin, carboplatin, cis-[PtCl(NH3)2(C8H17.NH2)], cis-[PtCl2(iPentNH2)2], cis-[PtCl2(C6H11NH2)2, DACH SS(II) and CHIP(IV) did not significantly damage DNA in cells. It was concluded that the interactions of these cisplatin analogues with DNA in human cells were strongly influenced by their ability to damage purified DNA.
authors.affiliation: School of Biochemistry and Molecular Genetics, University of New South Wales, Sydney, Australia. v.murray@unsw.edu.au
authors.forename: V
authors.initials: V
authors.lastname: Murray
authors.forename: J
authors.initials: J
authors.lastname: Whittaker
authors.forename: W D
authors.initials: WD
authors.lastname: McFadyen
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000032:analysis* / Q000187:drug effects / Q000302:isolation & purification; D004259:DNA-Directed DNA Polymerase / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D006367:HeLa Cells / Q000187:drug effects*; D006801:Humans; D009944:Organoplatinum Compounds / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D009944:Organoplatinum Compounds; D004259:DNA-Directed DNA Polymerase; D002945:Cisplatin; C049777:ormaplatin