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.