Cohen J D, Robins H I, Schmitt C L, Tanner M A
University of Wisconsin Clinical Cancer Center, Madison 53792.
Cancer Res. 1989 Nov 1;49(21):5805-9.
Using JM and MOLT3, two human T-cell acute lymphoblastic leukemia cell lines, we investigated the ability of 24-h thymidine exposures to enhance the cytotoxicity of cis-diammine-1,1-cyclobutane dicarboxylate platinum (II) (carboplatin). Clinically achievable thymidine concentrations (for 24 h) significantly enhanced carboplatin killing. Unexpectedly, thymidine-carboplatin enhancement was as great at a relatively low 200-micrograms thymidine/ml as at the clinically much more toxic range of 1000 micrograms/ml. For a constant thymidine concentration (500 micrograms/ml), thymidine-carboplatin interaction increased with longer thymidine exposures until about 16 to 24 h. Thymidine and 41.8 degrees C hyperthermia (for 1 h) together enhanced carboplatin killing significantly more than did hyperthermia-carboplatin or thymidine-carboplatin combinations. These results show that relatively brief, presumptively nonmyelosuppressive thymidine exposures can significantly increase carboplatin killing. Carboplatin-thymidine killing can then be further augmented by 41.8 degrees C hyperthermia.
我们使用两种人类T细胞急性淋巴细胞白血病细胞系JM和MOLT3，研究了24小时胸腺嘧啶核苷暴露增强顺二氨-1,1-环丁烷二羧酸铂（II）（卡铂）细胞毒性的能力。临床可达到的胸腺嘧啶核苷浓度（持续24小时）显著增强了卡铂的杀伤作用。出乎意料的是，在相对较低的200微克/毫升胸腺嘧啶核苷浓度下，胸腺嘧啶核苷-卡铂增强作用与临床毒性大得多的1000微克/毫升浓度下的增强作用一样大。对于恒定的胸腺嘧啶核苷浓度（500微克/毫升），胸腺嘧啶核苷-卡铂相互作用随着胸腺嘧啶核苷暴露时间延长而增加，直至约16至24小时。胸腺嘧啶核苷与41.8℃热疗（持续1小时）共同增强卡铂杀伤作用的程度显著高于热疗-卡铂或胸腺嘧啶核苷-卡铂组合。这些结果表明，相对短暂的、推测无骨髓抑制作用的胸腺嘧啶核苷暴露可显著增加卡铂的杀伤作用。然后，41.8℃热疗可进一步增强卡铂-胸腺嘧啶核苷的杀伤作用。
