Drug sensitivity spectra in Fanconi anemia lymphoblastoid cell lines of defined complementation groups
Drug sensitivity spectra in Fanconi anemia lymphoblastoid cell lines of defined complementation groups
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DOI：
10.1016/s0921-8777(99)00041-5
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发表时间：
1999-09-13
期刊：
影响因子：
--
通讯作者：
Buchwald, M
中科院分区：
文献类型：
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作者：
Carreau, M;Alon, N;Buchwald, M
范可尼贫血（FA）是几种遗传性疾病之一，其特征性细胞对DNA交联剂超敏，这表明FA蛋白可能作为DNA修复过程的一部分起作用。在临床层面，FA的特征是骨髓衰竭，影响儿童在早期。临床表型是异质性的，包括各种先天性畸形以及癌症易感性。FA患者分布在8个互补组，表明一个复杂的分子途径。八个可能的FA基因中的三个已经被克隆，尽管它们的功能还没有被确定。FA细胞对DNA交联剂（丝裂霉素C（MMC）和二环氧丁烷）高度敏感，在细胞系之间存在一些差异。尽管这些研究是使用遗传上未分类的FA细胞进行的，但在某些情况下已报告对单功能烷基化剂的敏感性。为了进一步分析和表征新鉴定的FA互补基团，我们测试了它们对UV辐射、单官能和双官能烷化剂以及对X射线模拟药物博来霉素的敏感性。我们发现FA互补基团D至H显示出对X射线模拟药物博来霉素的增加的敏感性。此外，除了对交联剂的特征敏感性之外，单一已知的FA-H细胞系还显示出对乙基乙烷磺酸盐（EMS）、甲基甲烷磺酸盐（MMS）的敏感性增加，这表明FA细胞中的药物敏感性谱更广。(C)1999 Elsevier Science B. V.保留所有权利。
Fanconi anemia (FA) is one of several genetic diseases with characteristic cellular hypersensitivity to DNA crosslinking agents which suggest that FA proteins may function as part of DNA repair processes. At the clinical level, FA is characterized by bone marrow failure that affects children at an early age. The clinical phenotype is heterogeneous and includes various congenital malformations as well as cancer predisposition. FA patients are distributed into eight complementation groups suggesting a complex molecular pathway. Three of the eight possible FA genes have been cloned, although their function(s) have not been identified. FA cells are highly sensitive to DNA crosslinking agents (mitomycin C (MMC) and diepoxybutane), with some variability between cell lines. Sensitivity to monofunctional alkylating agents has been reported in some cases, although these studies were performed with genetically unclassified FA cells. To further analyse and characterize the newly identified FA complementation groups, we tested their sensitivity to UV radiation, monofunctional and bifunctional alkylating agents and to the X-ray mimetic drug bleomycin, We found that FA complementation groups D to H show increased sensitivity to the X-ray mimetic drug bleomycin. Furthermore, the single known FA-H cell line shows increased sensitivity to ethylethane sulfonate (EMS), methylmethane sulfonate (MMS) in addition to the characteristic sensitivity to crosslinking agents, suggesting a broader spectrum of drug sensitivities in FA cells. (C) 1999 Elsevier Science B.V. All rights reserved.