Diatloff-Zito C, Rosselli F, Heddle J, Moustacchi E
CNRS URA 1292, Institut Curie, Paris, France.
Hum Genet. 1990 Dec;86(2):151-61. doi: 10.1007/BF00197697.
Transfectants obtained by mouse DNA-mediated gene transfer in Fanconi anemia (FA) primary fibroblasts from the genetic complementation groups A and B were examined for the frequencies of chromosomal aberrations and cytotoxicity following treatments by cross-linking agents. Cells from group A (FA 150), which is the most sensitive to such agents, are partially corrected for both the chromosomal and cellular hypersensitivity to 8-methoxypsoralen photoaddition. In contrast, after treatment with mitomycin C (MMC), only the chromosomal sensitivity is re-established to a near normal level. The opposite is true for FA group B cells (FA 145), i.e. cell survival to MMC is partially corrected, whereas the frequency of MMC-induced chromosomal aberration remains close to that of the untransfected cells. The partial phenotypic correction of the two end points examined is interpreted as indicating either a gene dosage effect or the necessity of introducing more than one gene type in order to achieve complete recovery of a normal phenotype. The phenotypic dissociation between the clastogenic and cellular hypersensitivity to cross-linking agents may offer the opportunity of isolating separately the responsible gene(s) by conventional rescue techniques.
通过小鼠DNA介导的基因转移，在来自A组和B组遗传性互补的范可尼贫血（FA）原代成纤维细胞中获得转染子，研究交联剂处理后染色体畸变频率和细胞毒性。A组（FA 150）细胞对这类试剂最为敏感，对8-甲氧基补骨脂素光加成的染色体和细胞超敏反应均得到部分校正。相比之下，用丝裂霉素C（MMC）处理后，仅染色体敏感性恢复到接近正常水平。B组FA细胞（FA 145）情况相反，即细胞对MMC的存活率得到部分校正，而MMC诱导的染色体畸变频率仍接近未转染细胞。所检测的两个终点的部分表型校正被解释为表明基因剂量效应，或为实现正常表型的完全恢复而引入不止一种基因类型的必要性。对交联剂的致断裂和细胞超敏反应之间的表型解离，可能为通过传统拯救技术分别分离相关基因提供机会。
