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Bromodeoxyuridine mutagenesis in mammalian cells is stimulated by thymidine and suppressed by deoxycytidine

Abstract

THE most widely accepted explanation for the mutagenicity of 5-bromodeoxyuridine (BUdR) is that mutations occur as the result of occasional mispairing of the analogue during DNA replication1,2, although the correlation between mutagenesis and the amount of bromouracil (BU) incorporated into DNA has been questioned3,4. We have previously shown that BUdR mutagenesis in Syrian hamster cells (measured by the induction of ouabain-resistant (OBr) or 6-thioguanine-resistant (TGr) mutants) is determined by the concentration of BUdR in the medium rather than the amount of BU in DNA5. This suggested that BUdR nucleotides are involved in BUdR mutagenicity in mammalian cells5 (see also ref. 4). BUdR triphosphate (BUdRTP) inhibits the ribonucleotide reductase-catalysed reduction of cytidine diphosphate to deoxycytidine (CdR) diphosphate6, as does thymidine (TdR) triphosphate (dTTP)7,8. Therefore, we have investigated the effects of CdR and TdR on BUdR mutagenesis, and report here that the former suppresses and the latter stimulates this process.

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DAVIDSON, R., KAUFMAN, E. Bromodeoxyuridine mutagenesis in mammalian cells is stimulated by thymidine and suppressed by deoxycytidine. Nature 276, 722–723 (1978). https://doi.org/10.1038/276722a0

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