Absence of misincorporation of pyrimidines in DNA after treatment with a combination of cisplatin (CIS-diammine-dichloro-platinum) amd 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 (CDDP), 5-fluorouracil (5-FU) or a combination of CDDP and 5-FU were studied in ascites sarcoma (Bp8) growing in mice. Single administration of CDDP gave an early (1 h) transient increase in the DNA-synthesis followed 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 and 5-FU markedly increased the rate of DNA synthesis up to 6 h as compared 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 detected. Hence, misincorporation of pyrimidines is not the mechanism for the synergistic effect of the combination of CDDP and 5-FU.
Nylén
U
U
Department of Oncology, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
Skog
S
S
Lewin
F
F
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects* / Q000378:metabolism*; D005472:Fluorouracil / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011743:Pyrimidines / Q000378:metabolism*; D012513:Sarcoma, Experimental / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D011743:Pyrimidines; D002945:Cisplatin; D005472:Fluorouracil