Study of the modifications caused by cisplatin, transplatin, and Pd(II) and Pt(II) mepirizole derivatives on pBR322 DNA by atomic force microscopy.

Modifications of the structure of pBR322 DNA caused by interaction with cisplatin, transplatin and Pd(II) and Pt(II) mepirizole derivatives were studied. The compounds were incubated with the plasmid DNA for 24 h at 37 degrees C and then observed with an atomic force microscope. Circular DNA was used because the small tertiary structural changes are easy to monitor. Likewise, its superhelical nature mimics DNA better than certain forms of intracellular DNA such as chromatin. AFM images clearly reveal that the complexes induce changes in the topological forms of fully relaxed pBR322 DNA. Most of the compounds produce a more compact DNA structure with modified writhing number. Analysis of gel migration of the relaxed pBR322 DNA incubated with the platinum complexes provides complementary information, which is in good agreement with AFM results.