Cancer Research Institute, Slovak Academy of Sciences, Špitálská 21, 812 32 Bratislava, Czechoslovakia
Cytotoxic synergism of cis-diamminedichloroplatinum (II) (cis-DDP) and arabinosylcytosine (ara-C) was studied both on the level of interaction with DNA in chemically determined conditions and en leukemia L1210 bearing mice. Ara-C and its structural natural prescursor cytidine were tested for the modulation of kinetics of bifunctional adducts production induced by cis-DDP in DNA. This process plays the basic role in cytotoxic mechanism and antitumor activity of cis-DDP. No interaction was seen between cis-DDP and ara-C. Presence of ara-C in reaction mixture had no effect on cis-DDP — DNA interaction. Therefore, cytotoxic synergism does not arise in the ara-C — cis-DDP — DNA interaction and its origin is different. Finding that cytidine has no synergistic effect on life span of leukemia L1210 bearing mice when administered together with cis-DDP shows the difference between cytidine and ara-C. The small stuctural difference between cytidine and ara-C is very important for synergism of cytotoxicity.
Synergism of Cis-DDP and ARA-C
