Nylén U, Skog S, Lewin F
Department of Oncology, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden.
Acta Oncol. 1996;35(2):229-35. doi: 10.3109/02841869609098506.
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.
研究了顺铂（CDDP）、5-氟尿嘧啶（5-FU）或CDDP与5-FU联合处理后，脱氧核糖核苷酸dCTP和dTTP掺入DNA的情况以及DNA合成速率，实验对象为在小鼠体内生长的腹水肉瘤（Bp8）。单次给予CDDP可使DNA合成在早期（1小时）短暂增加，随后下降。5-FU作为单一药物在6小时后确实会提高DNA合成速率，在10小时达到最大值。与单一药物治疗相比，CDDP和5-FU联合使用在长达6小时内显著提高了DNA合成速率。虽然联合治疗后dCTP池增加，而dTTP池不变，但未检测到掺入DNA的dTTP和dCTP比例有变化。因此，嘧啶的错误掺入不是CDDP和5-FU联合使用产生协同效应的机制。
