CAFFEINE DOES NOT POTENTIATE GAMMA-RADIATION INDUCED DNA-DAMAGE IN ATAXIA-TELANGIECTASIA LYMPHOBLASTOID-CELLS

Ataxia telangiectasia (AT) cells display a profound sensitivity to ion izing radiation, exhibiting more frequent chromosomal breaks, increase d micronuclei formation and abnormal DNA repair kinetics following exp osure. Despite the recent cloning of the ATM gene there remains a need for a simple and rapid means of discriminating AT heterozygotes from normal individuals. Caffeine (1,3,7-trimethyl xanthine), known to inhi bit the repair of double-strand DNA breaks following ionizing radiatio n, increases the frequency of radiation induced chromosomal breaks in normal cells. Here we report that caffeine potentiates the induction o f chromosomal breaks in G(2) arrested AT heterozygote and normal lymph oblastoid cells, but not in homozygous AT lymphoblastoid cells. This o bservation parallels the findings reported by others that caffeine fai ls to potentiate the effect of ionizing radiation in radiation-sensiti ve yeast strains and radiation sensitive CHO cells, It also suggests t hat caffeine may somehow mimic the effect of the ATM gene product in n ormal cells. We also report that caffeine is unlikely to be useful in helping to discriminate AT heterozygotes from normal individuals. (C) 1998 Elsevier Science B.V. All rights reserved.