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.

The relationship between BCL6 bodies and nuclear sites of normal and halogenated DNA and RNA synthesis

“…Indeed, IdU has been previously shown to be less efficiently incorporated in DNA than BrdU and CldU (Franken et al, 1997). On the other hand, it has been reported that modulating the concentration of BrdU in the medium favours the occurrence of damages in the replicating DNA by an imbalancing in the ratio between the nucleotide pools leading to frequent BrdU/ guanine mispairing (Davidson et al, 1980(Davidson et al, , 1988. However, the addition of deoxycytidine, which prevents such an effect, even in excess over BrdU or CldU (Davidson et al, 1988), does not affect the association of replicating (halogenated) DNA with BCL6 bodies (unpublished data), suggesting therefore that this association is indeed correlated with the level of incorporation of the halogenated nucleotide into the DNA.…”

The Distribution of Sister Chromatid Exchanges and Chromosomal Aberrations Induced by 5-Fluorodeoxyuridine and Ethyl Methanesulfonate in the Euchromatin and Heterochromatin of Chinese Hamster Cells

“…This may be due to the fact that the early S-phase was the stage most sensitive to the chemically induced SCEs, as shown in our results. The increased rate of SCEs after FUdR treatment in the present study may be explained by the hypothesis that SCE frequency depends to some extent on the BUdR concentration (4,9,11,19), and that FUdR inhibits thymidine synthesis which, thus producing efficient incorporation of BUdR into chromosomes (4,5).…”

Effect of deoxynucleosides on the frequency of sister chromatid exchanges in Bloom syndrome cells.

“…Deoxycytidine has been known to counteract an increase of SCEs by excess thymidine and BrdU in normal cells (Davidson et al, 1980;Kaufman, 1986). Purine deoxyribonucleosides (dG and dA) caused a significant concentration-dependent increased in SCE frequency both in normal and BS cells (Table I).…”