Formation and stability of interstrand cross-links induced by cis- and trans-diamminedichloroplatinum (II) in the DNA of Saccharomyces cerevisiae strains differing in repair capacity.
Four haploid yeast strains differing in proficiency for DNA repair were treated with cis- or transDDP. The wild type was least sensitive while the excision-deficient mutants rad1, rad2 and snm1 exhibited higher sensitivities to either platinum compound. In all four strains tested cisDDP showed a two- to five-fold higher cytotoxicity than equimolar concentrations of transDDP. DNA interstrand cross-linking was caused by both agents in all strains. However, transDDP introduced more DNA cross-links at exposure times up to 6 h while cisDDP was the more active cross-linking agent at longer times. There was no clear-cut correlation of the number of DNA interstrand cross-links with survival. Formaldehyde-treated cells showed DNA with lower buoyant density due to proteinase K sensitive DNA-protein cross-linking; this effect was not observed after treatment with either platinum compound. Post-treatment incubation of wild-type cells exposed to cisDDP led to degradation of DNA by single and double-strand breaks, parallel with further increase of DNA interstrand cross-linking. DNA from transDDP-treated cells did not show extensive degradation although interstrand cross-links were lost during liquid holding.
Wilborn
F
F
Institut für Mikrobiologie der J.W. Goethe-Universität, Frankfurt am Main, Federal Republic of Germany.
Brendel
M
M
D002499:Centrifugation, Density Gradient; D002945:Cisplatin / Q000494:pharmacology*; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004260:DNA Repair; D004271:DNA, Fungal / Q000378:metabolism*; D005557:Formaldehyde / Q000494:pharmacology; D005800:Genes, Fungal; D007536:Isomerism; D007700:Kinetics; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics*
D003432:Cross-Linking Reagents; D004271:DNA, Fungal; C034697:transplatin; D005557:Formaldehyde; D002945:Cisplatin