Effect of combined treatment with cisplatin and 5-fluorouracil on cell growth and cell cycle kinetics of a mouse ascites tumor growing in vivo.

The effect on cell growth and cell cycle kinetics of 0.8 mg cisplatin (CDDP)/kg body weight and 36 mg 5-fluorouracil (5-FU)/kg body weight given separately and in combination was studied on Bp8 mouse ascites sarcoma growing in vivo. Cell growth inhibition after combined treatment was delayed 12 hours but was persistent, while the cell growth inhibition was immediate after single drug treatment with a relative cell regrowth observed at the end of the observation period. The prolonged cell growth inhibition after combined treatment was probably due to cell death. Some cell kinetic interactions were found after combined treatment. An increased flow of cells from G1 was observed during the whole observation period. The depressed outflow of cells from S after single drug treatment was abolished during the first 24 hours following combined treatment. No prolongation was found on the CDDP-induced G2 delay. An increased relative number of cells in G2 following combined treatment was, however, found at 72 hours. This was due to an increased flow of cells from S to G2 seen after 48 hours. The molecular reasons and consequences are discussed.