Effects of ribonucleotides on cis-diamminedichloroplatinum(II) (cispla
tin)-mediated DNA damage were studied by incubating pUC18 DNA with cis
platin in the presence of nucleotide, and by monitoring conformational
change and sensitivity change to restriction enzyme HpaII of the DNA
due to the platinum-DNA adduct formation. The cisplatin-mediated DNA d
amage was inhibited in a dose-dependent fashion by ATP or GTP, substan
tially at their physiological intracellular concentrations, and almost
completely by 5 mM ATP or 2 mM GTP. The inhibitory effect of nucleoti
de on the platination of DNA was in the order of GTP > ATP much greate
r than CTP > UTP, and of nucleoside triphosphate > nucleoside diphosph
ate > nucleoside monophosphate. Nucleoside did not show any significan
t effect on platination of DNA. To elucidate the mechanism of the nucl
eotide effects on platination of DNA, interaction between ATP or GTP a
nd cisptatin was analyzed by high-performance liquid chromatography. T
he results suggested that ATP inhibits cisplatin-mediated DNA damage b
oth by forming a platinum-ATP adduct and by non-covalent ionic interac
tion with cisplatin, while GTP acts largely by forming platinum-GTP ad
ducts.