Persson L, Holm I, Ask A, Heby O
Department of Physiology, University of Lund, Sweden.
Cancer Res. 1988 Sep 1;48(17):4807-11.
The objective of the present investigation was to determine to what extent polyamine uptake from the host contributes to the ability of tumor cells in overcoming the antiproliferative effect of a polyamine synthesis inhibitor. A mutant L1210 leukemia cell line deficient in polyamine transport was isolated by selection for resistance to methylglyoxal bis(guanylhydrazone), an extremely cytotoxic agent which is taken up by the same transport system as the polyamines. C57BL/6 x DBA/2 F1 mice inoculated with mutant L1210 cells survived on the average 60 to 70% longer than mice inoculated with the parental cells. The therapeutic effect of a polyamine synthesis inhibitor, DL-2-difluoromethylornithine (3% in the drinking water), was much greater on mice bearing mutant L1210 cells (87% increase in median survival time; 13 of 40 mice cured) than on mice inoculated with parental cells (22% increase in median survival time). Similar results, although not as striking, were obtained using athymic nude mice, indicating that the therapeutic difference is not merely due to increased immunogenicity of the mutant cells.
本研究的目的是确定肿瘤细胞从宿主摄取多胺在多大程度上有助于其克服多胺合成抑制剂的抗增殖作用。通过选择对甲基乙二醛双（脒腙）具有抗性，分离出一种缺乏多胺转运功能的突变L1210白血病细胞系，甲基乙二醛双（脒腙）是一种极具细胞毒性的药物，它与多胺通过相同的转运系统进入细胞。接种突变L1210细胞的C57BL/6×DBA/2 F1小鼠的平均存活时间比接种亲代细胞的小鼠长60%至70%。多胺合成抑制剂DL-2-二氟甲基鸟氨酸（饮用水中含3%）对携带突变L1210细胞的小鼠的治疗效果（中位存活时间增加87%；40只小鼠中有13只治愈）比对接种亲代细胞的小鼠（中位存活时间增加22%）大得多。使用无胸腺裸鼠也得到了类似的结果，尽管不那么显著，这表明治疗差异不仅仅是由于突变细胞免疫原性的增加。
