McDaniel L D, Schultz R A
Medical Biotechnology Center, University of Maryland, Baltimore 21201.
Environ Mol Mutagen. 1993;21(1):67-72. doi: 10.1002/em.2850210109.
Aminoglycosides are a class of antibiotics that interfere with protein translation. Geneticin and hygromycin are two such agents, which have been shown to exhibit highly toxic effects in mammalian cells. Cloned bacterial genes, which inactivate these antibiotics, have facilitated the establishment of dominant selection systems, which are widely used in eukaryotic molecular genetics. We have examined the effect of aminoglycosides on the sister chromatid exchange (SCE) frequency in transformed human fibroblast cell lines. Geneticin and hygromycin were both found to increase SCE frequency in all cell lines examined, including a cell line derived from a patient with Bloom syndrome, a disorder exhibiting an elevated spontaneous SCE frequency. Induction was seen to occur in a dose-responsive manner and was also observed in cells expressing the resistance genes that inactivate the cellular toxicity of these antibiotics. The implications of these findings for somatic cell genetics and for human gene therapy protocols are discussed.
氨基糖苷类是一类干扰蛋白质翻译的抗生素。庆大霉素和潮霉素就是这样的两种药物，它们已被证明在哺乳动物细胞中表现出高度毒性作用。使这些抗生素失活的克隆细菌基因促进了显性选择系统的建立，该系统在真核分子遗传学中被广泛使用。我们已经研究了氨基糖苷类对转化的人成纤维细胞系中姐妹染色单体交换（SCE）频率的影响。发现庆大霉素和潮霉素在所有检测的细胞系中均增加SCE频率，包括来自一名患有布卢姆综合征患者的细胞系，该疾病表现出自发性SCE频率升高。诱导以剂量反应方式发生，并且在表达使这些抗生素的细胞毒性失活的抗性基因的细胞中也观察到。讨论了这些发现对体细胞遗传学和人类基因治疗方案的意义。
