ABSENCE OF MISINCORPORATION OF PYRIMIDINES IN DNA AFTER TREATMENT WITH A COMBINATION OF CISPLATIN (CIS-DIAMMINE-DICHLORO-PLATINUM) AND 5-FLUOROURACIL OF MOUSE SARCOMA-CELLS

The effects on incorporation into DNA of the deoxyribonucleotides dCTP and dTTP and the DNA synthesis rate after treatment with cisplatin (C DDP), 5-fluorouracil (5-FU) or a combination of CDDP and 5-FU were stu died in ascites sarcoma (Bp8) growing in mice, Single administration o f CDDP gave an early (1 h) transient increase in the DNA-synthesis fol lowed by a decrease. 5-FU as single agent did increase the rate of DNA synthesis after 6 h with a maximum at 10 h, The combination of CDDP a nd 5-FU markedly increased the rate of DNA synthesis up to 6 h as comp ared to single drug treatment, Although the dCTP pool increased after combined treatment, while the dTTP pool was unchanged, no alterations in the proportions of dTTP and dCTP incorporated into DNA could be det ected, Hence, misincorporation of pyrimidines is not the mechanism for the synergistic effect of the combination of CDDP and 5-FU.