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Nucleic Acids Research, 1984, Vol. 12, No. 22 8349-8362
© 1984

CHEMISTRY

Electron microscopic measurement of chain flexibility of poly(dG-dC.poly(dG-dC) modified by cis-diamminedichloroplatinum(II)

B. Revet1, J.M. Malinge3, E. Delain1, M.Le Bret2 and M. Leng3

1Laboratorie de Microscopie Cellulaire et Moléculaire 94805 Villejuif 2Laboratoire de Pharmacologie Moléculaire (LA 147 du CNRS), Institut Gustave-Roussy 94805 Villejuif 3Centre de Biophysique Moléculaire CNRS 45045, Orléans, France

Received August 29, 1984. Revised October 17, 1984. Accepted October 17, 1984.

The antitumor drug cis-diamminedichloroplatinum (II) (cis-Pt) forms bidentate adducts with guanine residues of poly(dG-dC).poly(dG-dC). The secondary structure of the polymer is altered. In this work, high resolution pictures of naked molecules, obtained by dark field electron microscopy reveal DNA chain distortions with radii as small as 30 Å. The extent of distortion increases with the drug/nucleotide ratio (rb). These alterations of the secondary structure are responsible for the apparent shortening of the molecules. Measurements of the persistence lengths of the polymer as well as the end-to-end distances of elementary segments of various lengths, are obtained from digitized eleotron micrographs. The measurements are used to monitor and quantify the observed modifications of polymer structure upon cis-Pt binding at various rb or incubation times. Poly(dG-m5dC) .poly(dG-m5dC) in the B and Z forms have different persistence lengths. In the B form, this polymer is more altered by cis-Pt than in the Z one.


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