In vivo enhancement of 5-fluorouracil cytotoxicity to AKR leukemia cells by thymidine in mice.
In vivo enhancement of 5-fluorouracil cytotoxicity to AKR leukemia cells by thymidine in mice.
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胸苷在小鼠体内增强 5-氟尿嘧啶对 AKR 白血病细胞的细胞毒性。
DOI：
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发表时间：
1978
期刊：
影响因子：
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通讯作者：
F. Valeriote
中科院分区：
文献类型：
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作者：
G. Santelli;F. Valeriote
采用脾集落形成法检测胸腺嘧啶核苷(DThd)对AKR(AKR小鼠)和L1210(BALB/c x DBA/2)F1小鼠移植瘤细胞毒作用的影响。大剂量的dThd(10 mg/只)不能将这些细胞株从Fura毒性中拯救出来。相反，当dThd在Fura之前1小时内给予时，它将AKR白血病中的Fura细胞毒性提高了100至1000倍。DThd仅使Fura对L1210白血病细胞的杀伤作用增加3倍，提示两种药物在两种细胞系中的相互作用机制不同。对能够支持两种白血病生长的杂交小鼠的检查表明，增强与肿瘤有关，而不是与宿主有关。我们还证实了AKR白血病患者在Fura前15分钟注射dThd的剂量依赖效应。关于Fura前15分钟给予dThd对AKR白血病集落形成单位(LCFU)的杀伤动力学，给药后24-36小时，LCFU存活率持续下降。
The spleen colony assay was used to examine the effect of thymidine (dThd) on 5-fluorouracil (FUra) cytotoxicity in two transplantable leukemias, AKR (in AKR mice) and L1210 [in (BALB/c x DBA/2)F1 mice], in vivo. A large dose of dThd (10 mg/mouse) could not rescue these cell lines from FUra toxicity. Instead, when dThd was given within 1 hour before FUra, it enhanced FUra cytotoxicity by a factor between 100 and 1,000 in AKR leukemia. That dThd increased the cytotoxicity of FUra only by a factor of 3 in L1210 leukemia suggested a different mechanism of interaction of the two drugs in the two cell lines. Examination in hybrid mice capable of supporting the growth of both leukemias showed the enhancement to be tumor related rather than host related. We also demonstrated a dose-dependent effect of dThd injection 15 minutes before FUra in AKR leukemia. Concerning the kinetics of killing of AKR leukemia colony-forming units (LCFU) following the administration of dThd 15 minutes before FUra, LCFU survival continued to decrease for 24--36 hours following drug administration.