The effect of 9-beta-D-arabinofuranosyladenine on the formation of X-ray induced chromatid aberrations in X-irradiated G2 human cells.
The effects of the nucleoside analogue 9-beta-D-arabinofuranosyladenine (are A) alone or in combination with X-rays on the induction of G2-phase chromosomal damage were studied in immortalized human fibroblasts of lung origin (MRC5-SV1). Ara A is known to be an S-phase specific clastogen, a powerful inhibitor of DNA synthesis and an inhibitor of DNA double-strand break (dsb) repair. The length of the G2-phase of this cell line could be defined as approximately 4 h from data for treatment of cells with ara A alone in which a sharp rise in number of chromatid aberrations was found to occur when ara A treatment times exceeded 4 h; i.e. when cells were in late S-phase at the time of treatment. The frequency of chromatid deletions in X-irradiated G2-phase cells was found to decrease as the time between irradiation and fixation increased. This was interpreted as reflecting the underlying repair of dsb. When X-irradiated cells were treated with ara A between irradiation and fixation, the decrease in deletions found after X-rays alone was not observed. This was interpreted as reflecting the inhibition of dsb repair. Unlike deletions, the yield of exchanges increased during incubation of G2-phase cells after X-ray exposure and the rate of this increase was found to be trebled by the addition of ara A to the medium. We postulate that the increased rate of exchange aberration formation in the absence of dsb repair indicates the existence of a second 'error-prone' misjoining mechanism which is independent of DNA synthesis.
Mozdarani
H
H
Department of Anatomy and Experimental Pathology, University of St Andrews, UK.
Bryant
P E
PE
D002460:Cell Line; D002869:Chromosome Aberrations; D002877:Chromosomes, Human / Q000187:drug effects / Q000528:radiation effects*; D006801:Humans; D007399:Interphase; D007700:Kinetics; D012854:Sister Chromatid Exchange; D014740:Vidarabine / Q000494:pharmacology*; D014965:X-Rays
D014740:Vidarabine