Elevation of sister chromatid exchange frequency in transformed human fibroblasts following exposure to widely used aminoglycosides.
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.
McDaniel
L D
LD
Medical Biotechnology Center, University of Maryland, Baltimore 21201.
Schultz
R A
RA
D002461:Cell Line, Transformed; D005347:Fibroblasts / Q000187:drug effects; D005839:Gentamicins / Q000633:toxicity*; D006801:Humans; D006921:Hygromycin B / Q000633:toxicity*; D009153:Mutagens / Q000633:toxicity*; D012044:Regression Analysis; D012854:Sister Chromatid Exchange; D014407:Tumor Cells, Cultured / Q000187:drug effects
D005839:Gentamicins; D009153:Mutagens; D006921:Hygromycin B; C010680:antibiotic G 418