Effects of the nucleoside analogues 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

Abstract

The effects of the DNA polymerase inhibitors a-ara A and beta-ara C have been 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, a-ara A was found to have 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 two drugs to cause fixation or misrepair of the DNA double strand breaks during or after treatment with the drugs.