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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

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Summary

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 snm1exhibited 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.

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  1. Institut für Mikrobiologie der J. W. Goethe-Universität, Theodor-Stern-Kai 7, D-6000, Frankfurt am Main, Germany

    Freimut Wilborn & Martin Brendel

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  1. Freimut Wilborn
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  2. Martin Brendel
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Wilborn, F., Brendel, M. 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. Curr Genet 16, 331–338 (1989). https://doi.org/10.1007/BF00340711

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  • DOI: https://doi.org/10.1007/BF00340711

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