THE ANTI Z-DNA REACTIVITY OF Z-DNA FORMING SEQUENCES IS AFFECTED BY PLATINUM ANTITUMOR DRUGS

The effect of binding of platinum antitumor drugs, cis-diamminedichlor oplatinum (II) (cis-DDP) and Pt-pentamidine, on the Z-DNA reactivity o f potential Z-DNA forming sequences has been studied by enzyme-linked immunosorbent assay. rhe results indicate that cis-DDP and Pt-pentamid ine increase the Z-DNA reactivity of plasmids containing a (dG-dC)16 i nsert (pUCZ8) and a native Z-DNA forming sequence of Drosophila hydei (pF18). The molar ratio of platinum bound to nucleotides (r(b)) to pro duce 50% of Z-DNA reactivity was 0.10 for cis-DDP:pF18, 0.15 for Pt-pe ntamidine: pF18, and 0.10 for cis-DDP:pUCZ8 and Pt-pentamidine:pUCZ8. The efficacy of Pt-pentamidine to provoke Z-DNA reactivity is 2.5-fold higher than that of cis-DDP. While Pt-pentamidine was capable of indu cing Z-DNA reactivity in a GC-rich DNA sequence of the hsp 70 protein of Trypanosoma cruzi (p2M4EO3) and in sequences of pUC8, cis-DDP suppr esses Z-DNA reactivity. CD spectra of poly(dG-me5dC). poly(dG-me5dC) m odified by the drugs suggest that the increase in Z-DNA reactivity obs erved in plasmids upon drug binding may be due to shifting towards Z-D NA or a Z-DNA like conformation