Effect of cis-diammino-dichloro-platinum (II) on cell growth and cell cycle progression of a mouse ascites tumor growing in vivo.
Cell kinetic studies of cis-platin (CDDP) have been few with divergent results. In this study, the effect of 12.5 and 25 micrograms CDDP/animal corresponding to approximately 0.4 and 0.8 mg CDDP/kg body weight was described when treating the Bp8 ascites sarcoma growing in mice. From sequential studies of the total number of cells together with the composition of cells in the cell cycle, the flow of cells through the cell cycle was calculated. A dose-dependent cell growth inhibition was found with almost immediate effect following the higher dose, while an inhibitory effect on cell growth with the lower dose was delayed 24 hours. The cell flow from the various phases of the cell cycle for the first 24.48 hours following administration of the lower dose, was increased from the G1-phase and mitosis, with normal flow from the S-phase and depressed outflow from the G2-phase. Thereafter the flow rates from all cell cycle phases were decreased. For the higher dose, the outflow rates from all phases of the cell cycle were depressed up to 72 hours. The maximum platination of DNA was found one hour after treatment. The results indicate that the mechanisms responsible for the passage through the G2 stage of the cell cycle are more sensitive to the treatment of CDDP than replicative DNA synthesis. This experimental system may be used as a basis for further mechanistic studies of the antitumor effect of anticancer drugs.
Lewin
F
F
Department of Medical Radiobiology, Karolinska Institute, Stockholm, Sweden.
Skog
S
S
Tribukait
B
B
Ringborg
U
U
D000818:Animals; D001201:Ascites; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D004273:DNA, Neoplasm / Q000032:analysis / Q000378:metabolism; D003979:Diazonium Compounds / Q000138:chemical synthesis / Q000633:toxicity*; D016193:G1 Phase / Q000187:drug effects; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008938:Mitosis / Q000187:drug effects; D016196:S Phase / Q000187:drug effects; D012513:Sarcoma, Experimental / Q000188:drug therapy / Q000473:pathology*
D004273:DNA, Neoplasm; D003979:Diazonium Compounds; C072609:4-methylbenzenediazonium; D002945:Cisplatin