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应用递增浓度的方法建立了一株顺铂（ＣＤＤＰ）耐药细胞系Ａ５４９ＤＤＰ。用溴化乙啶荧光分光光度法测定细胞内Ｐｔ－ＤＮＡ链间交联物（ＩＣＬ）；用无焰原子吸收光谱法测定细胞浆内及细胞核内铂含量；用流式细胞法及荧光显微镜测定铂的外排速度。结果显示：耐药细胞Ａ５４９ＤＤＰ较亲代敏感细胞Ａ５４９对ＣＤＤＰ耐受性增加８．９倍，与亲代敏感细胞Ａ５４９相比，Ａ５４９ＤＤＰ胞浆内及核内ＣＤＤＰ积聚分别为亲代细胞的１６．９％与２４．３％，铂含量与ＣＤＤＰ浓度正相关；Ａ５４９ＤＤＰ外排ＣＤＤＰ的功能较Ａ５４９明显增强，ＩＣＬ形成量低８４．１％，而修复功能增强２倍。结果提示：Ａ５４９ＤＤＰ细胞内ＣＤＤＰ积聚减少和修复功能增强是ＣＤＤＰ的主要耐药机理。
A cisplatin (CDDP)-resistant cell line, A549DDP, was established using increasing concentrations. The intracellular Pt-DNA interstrand crosslinker (ICL) was measured by ethidium bromide fluorescence spectrophotometry; the platinum content in the cytoplasm and in the nucleus was measured by flameless atomic absorption spectrometry; and determined by flow cytometry and fluorescence microscopy. Platinum out speed. The results showed that the A549DDP-resistant cells had a 8.9-fold increased tolerance to CDDP compared with the parental sensitive cell line A549. Compared with the parental sensitive cell line A549, the intracytoplasmic and nuclear CDDP accumulation of A549DDP was 16.9% of the parental cells, respectively. At 24.3%, the platinum content was positively correlated with the CDDP concentration; the function of the A549DDP efflux CDDP was significantly higher than that of the A549, the ICL formation was 84.1% lower, and the repair function was doubled. The results suggest that the decrease of CDDP accumulation and the enhancement of repair function in A549 DDP cells are the main drug resistance mechanism of CDDP.