Induction of sister chromatid exchanges by BUdR is largely independent of the BUdR content of DNA

Abstract

The halogenated thymidine (dT) analogue, 5-bromodeoxy-uridine (BUdR), has a variety of effects on mammalian cells, including toxicity, suppression of differentiation, and mutagenesis. Although it is generally assumed that the effects of BUdR are due primarily to its presence in DNA, results from our laboratory have raised doubts about such assumptions. We have shown, for example, that BUdR mutagenesis in mammalian cells is determined by the concentration of BUdR in the medium rather than in DNA, and that mutagenesis can be suppressed by deoxycytidine (dC) without changing the amount of BUdR in DNA. BUdR has also been shown to induce sister chromatid exchanges (SCEs) in mammalian cells. Initial results suggested that the relationship between BUdR and SCEs might not be explained by a single factor, and various correlations between BUdR and SCEs have been proposed. However, the results to date have been inconclusive, because the experiments did not resolve as independent variables the concentration of BUdR in the medium and the amount of BUdR incorporated into nuclear DNA. We have now carried out experiments to resolve these two factors; the results indicate that the major factor in determining the frequency of SCEs is the concentration of BUdR in the medium.