L1210／DDP细胞交叉耐药性及耐药机制的初步研究

目的观察小鼠淋巴细胞白血病顺铂耐药细胞亚系（L1210／DDP）与其它抗癌药物的交叉耐药性及对耐药机制进行初步研究。方法用拒染法测定细胞对不同抗癌药物的敏感性，用无火焰原子吸收光谱仪、谷胱甘肽还原酶循环法和微孔滤膜碱洗脱技术分别测定细胞内铂离子浓度、总谷胱甘肽含量、谷胱甘肽s-转移酶活性以及细胞DNA链间交联效应。结果L1210／DDP对卡铂有明显的交叉耐药性，对丝裂霉素、噻替派具有部分交叉耐药性，对阿霉素和5-氟尿嘧啶等无交叉耐药性。L1210／DDP细胞内的铂离子浓度和DNA链间交联指数明显低于L1210细胞，总谷胱甘肽含量、谷胱甘肽s-转移酶活性明显高于L1210细胞。结论L1210／DDP细胞亚系对DDP的结构类似物卡铂具有明显的交叉耐药性，其耐药机制与降低细胞内铂离子浓度、升高总谷胱甘肽含量和谷胱甘肽s-转移酶活性、降低DNA链间交联效应有关。

Cross-resistance of L1210/DDP Cell and its Possible Mechanism

Aim To observe the cross-resistance of the cell subline resisting to DDP (L1210/DDP) and its possible mechanism. Methods Drug sensitivity was determined by dye exclusion assay. The concentration of Pt and glutathionin, activity of glutathione transferase and cross-link of DNA were compared using a non-flare atomic absorption spectrometer,a circulation method of glutathione transferase and alkali washing with micropore film. Results L1210/DDP was cross-resistant to carboplatin, partly resistant to mitomycin and thiotepa, but sensitive to arabinosylcytosin and 5-fluorouracil. The Pt concentration in L1210/DDP was significant lower than that in L1210. The concentration of glutathionin as well as the activity of glutathione transferase in the subline was markedly higher than those of the maternal line. The cross-link of DNA in L1210 under DDP treatment was lower than that in the maternal line. Conclusion L1210/DDP was resistant to DDP and carboplatin, and its possible mechanism might be related to reduced Pt concentration, elevated the concentration of glutathionin and the activity of glutathione transferase, and decreasing crosslink of DNA.