人膀胱癌耐药细胞株p53基因突变与染色体畸变的关系

目的：研究膀胱癌耐药细胞株p53蛋白表达，探讨其与细胞染色体变化特点及耐药性的关系。方法：使用药物深度递增的方法，分别采用阿霉素（ADM）或足叶乙甙（VP－16）建立了人膀胱癌耐药细胞株BIU－87／A和BIU－87／V，采用免疫组织化学的方法对比分析其和亲代细胞株p53蛋白表达情况，并用G显带法研究各株细胞染色体特点。结果：BIU－87／A对ADM、VP－16的耐药倍数分别为57．42、59．40；BIU－87／V对ADM、VP－16的耐药倍数分别为6．45、5．44。BIU－87的p53蛋白表达阴性，而BIU－87／A、BIU－87／V的p53蛋白均阳性，且BIU－87／A的表达量多于BIU－87／V。BIU－87／A和BIU－87／V细胞染色体数目为超三倍体，染色体众数分别为78、73，数目在50－113之间，大多数染色体均有数目异常，变动于1－4条之间，染色体缺失、突变、到位、易位和环状染色体等结构畸形明显多于亲本细胞。结论：膀胱肿瘤耐药细胞株p53的异常表达可导致细胞染色体畸变增加，并与细胞多药耐药性与有一定的关系。

The relationship between p53 mutation in drug-resistance lines of bladder cancer and chromosome aberration

Objective To study the relationship among expression of p53 protein in drug resistant lines of bladder cancer and chromosome aberration,multidrug resistant characteristics.Methods Drug resistant lines BIU 87/A or BIU 87/V were established by continuous selection from human bladder cancer cell line BIU 87 cultured in medium by increasing doses of adriamycin (ADM) and etoposide (VP 16) respectively.Protein products of p53 were detected by immunohistochemical method and chromosome characteristic were analyzed by G display method in cell lines.Results The BIU 87/A cell was 57.42,59.40 times more resistant to ADM,VP 16 than the BIU 87 parent cells; The BIU 87/V cell was 6.45, 5.44 times more resistant to ADM and VP 16.p53 proteins were negative in BIU 87 cell but positive in BIU 87/A and BIU 87/V cells.The expression levels of p53 in BIU 87/A were significantly higher than in BIU 87/V.The sum of chromosome of BIU 87/A and BIU 87/V were super triploid.The numbers of chromosome were between 50 and 113,and the modal numbers were 78 and 73 respectively.Most chromosome's numbers were abnormal,changing between 1 and 4.The deletion,mutation,translocation,and crico chromosome in the multidrug resistant cells were more than parent cells.Conclusion Abnormal expression of mutate p53 in drug-resistant lines of bladder cancer may result in augmentation of chromosome aberration,and may lead to multidrug resistance of cells.