Atomic force microscopy examination of conformations of polynucleotides inresponse to platinum isomers: Significance of GC content at broken ends

Atomic force microscopy is a technique that enables visualization of macrom olecular conformations of polynucleotides at nanometer resolution. We inves tigated the results of interactions of cisplatin, a DNA binding anticancer drug, and its inactive counterpart, transplatin isomer, on the molecular co nformation of polynucleotides: poly d(G-C) . poly d(G-C) (polyGC) and poly d(A-T) . poly d(A-T) (polyAT). We observed that polyAT exhibited an increas ed number of enlarged ends of molecules, which we attribute to unwound and/ or collapsed regions of polyAT. PolyGC molecules did not show such ends unl ess cisplatin was added to the PolyGC polymers. Transplatin had the apparen t effect of causing overlapping or stacking of the polymer molecules. Addit ion of exonuclease-III to these polymers removed the visible enlarged ends. The effects of cisplatin as compared to transplatin on the polyGC duplex p olymers provide support for the presence of intrastrand covalent linkages, consistent with known N7 guanine interaction of the cis isomer on molecular conformation. Furthermore, our results indicate that the mechanism of inte ractions of DNA with cisplatin may be dependent on the GC content of the mo lecules. Int J. Cancer (Radiat. Oncol. Invest.) 90, 68-72, 2000. (C) 2000 W iley-Liss, Inc.