The effect of 9-β-D-arabinofuranosyladenine on the formation of X-ray induced chromatid aberrations in X-irradiated G2 human cells

The effects of the nucleoside analogue 9-β-D-arabinofuranosyladenine (ara 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). 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. The authors 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. (author)