on the effects of ara-a and ara-c on x-ray induced dna lesions in normal human and a-t cells: similarities and differences.

a better understanding of the mechanism of chromosomal aberration formation could be obtained by using dna repair inhibitors. immortalized normal human (mrc 5 svi) and ataxia telangiectasia ( at 5 biv a ) fibroblastic cell lines were treated with adenosine arabinoside (ara-a) and cytosine arabinoside (ara-c), both potent inhibitors of dna dsb repair, alone or in combination with x-rays at g2 or s-phase of the cell cycle. the length of g2-phase for both cell lines was determined by autoradiographic labeling to be about 4.5-5 h. a similar result was obtained by scoring of chromosomally damaged cells following treatment with ara-a or ara-c for various time intervals before fixation. the results obtained in this study show that in spite of many similarities between the action of ara-a and ara-c, e.g., inhibition of dna synthesis ciastogenic effects at g2 and s-phase and also lack of synergism as a possible consequence of these similarities, ara-a was found to have a different effect on rejoining of x-ray induced dna lesions than that of ara-c. ara-a caused inhibition of chromatid deletion rejoining, interpreted as inhibition of rejoining of dna dsb at all sampling times before fixation, whereas ara-c showed a synergistic effect on radiation-induced dna lesions, resulting in an increased frequency of chromatid deletions. thus there appears that these inhibitors have different modes of action on x-ray induced dna lesions, which may suggest a peculiar and important difference in the nature of these two nucieosides.