Evaluation of synergism of drugs cis-diamminedichloroplatinum (II) and arabinosylcytosine on the level of chemical interaction with DNA and on the growth of mouse leukemia.
1. Cytotoxic synergism of drugs cis-diamminedichloroplatinum(II) (cis-DDP) and arabinosylcytosine (araC) was studied both on the level of interaction with DNA in chemically determined conditions and on leukemia L1210 bearing mice. 2. AraC and its structural natural precursor cytidine were tested for the modulation of kinetics of bifunctional adducts production induced by cis-DDP in DNA. 3. This process plays the basic role in cytotoxic mechanism and antitumor activity of cis-DDP. 4. No interaction was seen between cis-DDP and araC. Further, presence of araC in reaction mixture had no effect on cis-DDP-DNA interaction. 5. Therefore, cytotoxic synergism does not arise in the araC-cis-DDP-DNA interaction and its origin is different. 6. Finding that cytidine has no synergistic effect on life span of leukemia L1210 bearing mice when administered together with cis-DDP it shows the difference between cytidine and araC. 7. The small structural difference between cytidine and araC is very important for synergism of cytotoxicity.
Rauko
P
P
Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Czechoslovakia.
Novotný
L
L
Reichelová
V
V
Balázová
E
E
D000818:Animals; D002945:Cisplatin / Q000494:pharmacology* / Q000633:toxicity; D003561:Cytarabine / Q000494:pharmacology* / Q000633:toxicity; D003562:Cytidine / Q000378:metabolism; D004273:DNA, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D005260:Female; D005456:Fluorescent Dyes; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D013056:Spectrophotometry, Ultraviolet
D004273:DNA, Neoplasm; D005456:Fluorescent Dyes; D003561:Cytarabine; D003562:Cytidine; D002945:Cisplatin