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为研究人类乳腺癌细胞抗药性和突变率的差异及产生机理，作者检测了同来源于ＭＤＡ－ＭＢ－４３５的人类乳腺癌细胞Ｌ－２和Ｂｒ－１的突变率和对药物ＰＡＬＡ的敏感性，并用流式细胞仪测定两细胞株经ＰＡＬＡ处理后细胞周期分布的变化，用ＤＮＡ碎片法研究细胞凋亡，及用ＷｅｓｔｅｒｎＢｌｏｔ测定Ｐ５３蛋白的表达。结果显示：Ｌ－２和Ｂｒ－１细胞的突变率和对ＰＡＬＡ的敏感性存在巨大差异；经ＰＡＬＡ处理后，两细胞株皆表现出细胞周期滞留在Ｓ期，但Ｌ－２细胞开始出现细胞凋亡而Ｂｒ－１细胞仍能存活。在去除培养液中的ＰＡＬＡ后，Ｂｒ－１细胞能恢复正常细胞周期和生长，而Ｌ－２细胞则一直停留在Ｓ期并继续细胞凋亡；在ＰＡＬＡ处理两细胞的过程中都未检测到Ｐ５３蛋白表达的变化。以上结果表明，一种非ｐ５３依赖型的细胞周期Ｓ期滞留启动的细胞凋亡机理，是造成Ｌ－２和Ｂｒ－１乳腺癌细胞抗药性和突变率差异的原因。
To investigate the differences in the resistance and mutation rate of human breast cancer cells and the mechanism of their production, the authors examined the mutation rates of L-2 and Br-1 in human breast cancer cells derived from MDA-MB-435 and their susceptibility to drug PALA. The cell cycle distribution of PALA-treated cells was measured by flow cytometry. Apoptosis was detected by DNA fragmentation method, and the expression of P53 protein was determined by Western Blot. The results showed that the mutation rate of L-2 and Br-1 cells and the sensitivity to PALA were greatly different; after treatment with PALA, both cell lines showed cell cycle retention in S phase, but L-2 cells began to appear cells. Apoptosis and Br-1 cells can still survive. After removal of PALA from the culture medium, Br-1 cells restored normal cell cycle and growth, whereas L-2 cells remained in S phase and continued to undergo apoptosis; neither of them was detected during the PALA treatment of two cells. Changes in P53 protein expression. The above results indicate that a non-p53-dependent mechanism of cell cycle initiation induced by S-phase arrest is responsible for the differences in drug resistance and mutation rate of L-2 and Br-1 breast cancer cells.