EFFECTS OF THE NUCLEOSIDE ANALOGS ALPHA-ARA-A, BETA-ARA-A AND BETA-ARA-C ON CELL-GROWTH AND REPAIR OF BOTH POTENTIALLY LETHAL DAMAGE AND DNA DOUBLE STRAND BREAKS IN MAMMALIAN-CELLS IN CULTURE

  • 1 January 1983
    • journal article
    • research article
    • Vol. 3  (2) , 143-149
Abstract
The effects of the DNA polymerase inhibitors .alpha.-ara A (.alpha.-arabinofuranosyladenine) and .beta.-ara C (.beta.-arabinofuranosylcytosine) were compared with those of .beta.-ara A on the endpoints of cell growth, repair of X-ray induced potentially lethal damage (PLD) and repair of X-ray induced DNA double strand breaks [in mouse Ehrlich ascites tumor cells]. .alpha.-Ara-A had no effects on any of the endpoints studied. .beta.-ara C inhibited cell growth and DNA double strand breaks repair more strongly than .beta.-ara A, but it was less effective in inhibiting repair of PLD. The inhibition of PLD repair by .beta.-ara C resulted in a diminution of the shoulder width of the X-ray survival curve, a result similar to that previously found for .beta.-ara A. The effectiveness of .beta.-ara C was enhanced when cells were treated with the drug in fresh medium rather than under plateau phase conditions. The lower effectiveness of .beta.-ara C, when compared with .beta.-ara A in causing expression of PLD, is interpreted in terms of a difference in the ability of the 2 drugs to cause fixation or misrepair of the DNA double strand breaks during or after treatment with the drugs.