Cytogenetic response of normal human and ataxia telangiectasia G2 cells exposed to X-rays and ara C.
The kinetics of rejoining of chromatid deletions and the formation of exchanges has been studied in X-irradiated normal and ataxia telangiectasia (AT) fibroblasts treated in the presence or absence of the nucleoside analogue 1-beta-D-arabinofuranosylcytosine (ara C). Ara C is a powerful inhibitor of DNA synthesis as well as an inhibitor of DNA double-strand break repair. Treatment with ara C was found to increase the frequency of X-ray-induced chromatid deletions in both lines with increasing incubation time while deletions were found to rejoin with first-order kinetics and a t1/2 of 2.4-3.1 h in both cell lines. The increase in deletions in the presence of ara C is thought to be due to an interaction of ara C-induced lesions (as yet unidentified) with lesions induced by X-rays, leading to additional chromatid breaks. These results are in contrast to those previously obtained with the same lines treated with X-rays and 9-beta-D-arabinofuranosyladenine (ara A). In this case the frequency of deletions in X-irradiated cells remained constant in both lines in the presence of ara A. We therefore propose that there is a major difference in the mode of action of ara C and ara A on X-ray-induced DNA damage in G2 cells. Exchanges were formed in X-irradiated cells in the presence and absence of ara C in both lines and the frequency increased with post-irradiation incubation time. A higher frequency was formed in ara C-treated cells than in cells given X-rays alone, but the enhancement by ara C was less than that previously found in cells treated with ara A.
Department of Biology and Preclinical Medicine, St. Andrews University, Fife, U.K.
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Mozdarani
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Bryant
D001260:Ataxia Telangiectasia / Q000235:genetics*; D002460:Cell Line; D002869:Chromosome Aberrations / Q000187:drug effects*; D003561:Cytarabine / Q000633:toxicity*; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007399:Interphase; D007700:Kinetics; D012854:Sister Chromatid Exchange / Q000187:drug effects / Q000528:radiation effects; D014740:Vidarabine / Q000633:toxicity
D003561:Cytarabine; D014740:Vidarabine