Enhanced expression of X-ray- and UV-induced chromosome aberrations by cytosine arabinoside in ataxia telangiectasia cells.
The effect of cytosine arabinoside (ara-C) on the frequency of X-ray- or UV-induced chromosome aberrations was studied in cultured skin fibroblasts derived from 2 normal persons, 4 ataxia telangiectasia (AT) patients and 2 obligate AT heterozygotes. Density-inhibited cells were irradiated with X-rays or UV, post-treated with ara-C, and chromosomes in the first post-irradiation mitoses were examined. UV, a poor inducer of chromosome-type aberrations in G1, caused chromosome-type aberrations (dicentrics and rings) when coupled with ara-C both in normal and AT cells, but to a much greater extent in AT cells. In AT cells, an elevated induction of both terminal deletions and chromatid aberrations was also observed by the application of UV and ara-C, and unexpectedly, UV alone induced a considerable frequency of both types of aberrations. The enhancing effect of ara-C on X-irradiated cells was less pronounced than on UV-irradiated cells. The responses of AT heterozygotes were virtually the same as those of normal cells. These findings suggest that ara-C can convert the UV-induced DNA damage into the type that has a potential to induce dicentrics and rings in G1 as well as to elicit a hypersensitive response of AT cells.
D001260:Ataxia Telangiectasia / Q000235:genetics*; D002478:Cells, Cultured; D002842:Chromatids / Q000187:drug effects; D002869:Chromosome Aberrations; D002872:Chromosome Deletion / Q000187:drug effects; D003561:Cytarabine / Q000633:toxicity*; D004260:DNA Repair / Q000187:drug effects*; D006801:Humans; D009154:Mutation / Q000187:drug effects / Q000528:radiation effects*; D012867:Skin / Q000166:cytology; D014466:Ultraviolet Rays; D014965:X-Rays
D003561:Cytarabine