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人膀胱和睾丸肿瘤连续细胞系中铂-DNA加合物的差异修复

Differential repair of platinum-DNA adducts in human bladder and testicular tumor continuous cell lines.

作者信息

Bedford P, Fichtinger-Schepman A M, Shellard S A, Walker M C, Masters J R, Hill B T

机构信息

Laboratory of Cellular Chemotherapy, Imperial Cancer Research Fund Laboratories, Lincoln's Inn Fields, London, United Kingdom.

出版信息

Cancer Res. 1988 Jun 1;48(11):3019-24.

PMID:3365691
Abstract

The formation and removal of four platinum-DNA adducts were immunochemically quantitated in cultured cells derived from a human bladder carcinoma cell line (RT112) and from two lines derived from germ cell tumors of the testis (833K and SUSA), following exposure in vitro to 16.7 microM (5 micrograms/ml) cisplatin. RT112 cells were least sensitive to the drug and were proficient in the repair of all four adducts, whereas SUSA cells, which were 5-fold more sensitive, were deficient in the repair of DNA-DNA intrastrand cross-links in the sequences pApG and pGpG. Despite expressing a similar sensitivity to SUSA cells, 833K cells were proficient in the repair of all four adducts, although less so than the RT112 bladder tumor cells. In addition, SUSA cells were unable to repair DNA-DNA interstrand cross-links whereas 50-85% of these lesions were removed in RT112 and 833K cells 24 h following drug exposure. It is possible that the inability of SuSa cells to repair platinated DNA may account for their hypersensitivity to cisplatin.

摘要

在体外暴露于16.7微摩尔(5微克/毫升)顺铂后,采用免疫化学方法对源自人膀胱癌细胞系(RT112)以及源自睾丸生殖细胞瘤的两个细胞系(833K和SUSA)的培养细胞中四种铂-DNA加合物的形成和去除情况进行了定量分析。RT112细胞对该药物最不敏感,且对所有四种加合物的修复能力良好,而敏感性高5倍的SUSA细胞在修复pApG和pGpG序列中的DNA-DNA链内交联方面存在缺陷。尽管833K细胞对顺铂的敏感性与SUSA细胞相似,但它对所有四种加合物的修复能力良好,不过比RT112膀胱肿瘤细胞要弱。此外,SUSA细胞无法修复DNA-DNA链间交联,而在药物暴露24小时后,RT112和833K细胞中50%-85%的此类损伤能够被修复。SUSA细胞无法修复铂化DNA的情况可能是其对顺铂超敏的原因。

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