The differences between cis- and trans-diamminedichloroplatinum II (DDP) in
forming DNA-protein cross-links in isolated human lymphocytes were investi
gated. Both cis- and trans-DDP can induce DNA-protein cross-links. We show
that cis-DDP forms complexes between DNA and proteins faster than trans-DDP
. This results from an increase in the quantity of DNA and platinum togethe
r with an increase in drug concentration. Under the same conditions trans-D
DP causes a decrease in DNA-forming complexes with proteins. After a 12 h i
ncubation of lymphocytes we observe a similar level of DNA in DNA-protein c
rosslinks induced by DDP isomers, but more platinum appears in complexes in
duced by trans-DDP. The results obtained demonstrate that the antitumor dru
g - cis-DDP and the clinically ineffective trans-DDP induce links between D
NA and proteins in a different manner. We suggest that the therapeutic acti
vity of cis-DDP can in part arise from rapidly forming DNA-protein complexe
s which can destroy the most important cellular processes, such as replicat
ion and transcription.