Biophysical studies of the modification of DNA by antitumour platinum coordination complexes.
Cisplatin (cis-diamminedichloroplatinum(II] is widely used in the treatment of various human tumours. A large body of experimental evidence indicates that the reaction of cisplatin with DNA is responsible for the cytostatic action of this drug. Several platinum-DNA adducts have been identified and their effect on the conformation of DNA has been investigated. Structural studies of platinum-DNA adducts now permit a reasonably good explanation of the biophysical properties of platinated DNA. Antitumouractive platinum compounds induce in DNA, at low levels of binding, local conformational alterations which have the character of non-denaturing distortions. It is likely that these changes occur in DNA due to the formation of intrastrand cross-links between two adjacent purine residues. On the other hand, the modification of DNA by antitumour-inactive complexes results in the formation of more severe local denaturation changes. Conformational alterations induced in DNA by antitumour-active platinum compounds may be reparable with greater difficulty than those induced by the inactive complexes. Alternatively, non-denaturation change induced in DNA by antitumour platinum drugs could represent more significant steric hindrance against DNA replication as compared with inactive complexes.
Institute of Biophysics, Czechoslovak Academy of Sciences, Brno.
V
V
Brabec
V
V
Kleinwächter
J L
JL
Butour
N P
NP
Johnson
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D006801:Humans; D009944:Organoplatinum Compounds / Q000378:metabolism / Q000494:pharmacology*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D004247:DNA