Kinetics of the reaction of cis-platinum compounds with DNA in vitro.

The kinetics of the reaction of a series of cis-platinum(II) compounds with DNA in vitro has been studied using their ability to disturb the secondary structure of the macromolecule. The complexation modifies the stacking of the base pairs and causes an inhibition of the intercalation of ethidium bromide which is correlated with the number of platinum atoms bound per nucleotide. The compounds fall into three groups which react in a few minutes, in a few hours or in several days. The inhibition of the complexation by chloride and carboxylato ions indicates that the interaction occurs through hydrolysed species and that hydrolysis is the rate limiting step. In addition the results indicate that the carboxylato entities are able to react with DNA in vitro without enzymatic activation and that there is no correlation between the antitumoral activity of these compounds against L1210 Leukemia cells and their in vitro reactivity towards DNA.