Sister chromatid exchange formation in mammalian cells is modulated by deoxyribonucleotide pool imbalance

The formation of sister chromatid exchanges (SEC) is closely related to DNA replication which is dependent on the proper balance of deoxyribonucleic triphosphates. Since DNA precursor imbalances can influence DNA metabolism, the relationship between 5-bromodeoxyuridine (BrdUrd)-induction of SCE and nucleotide pool imbalance was examined in Syrian hamster fetal cells (HFC) and mouse 3T6 cell line. In exponentially growing HFC, deoxyadenosine and deoxyguanosine stimulated the formation of SCE, while deoxycytidine (dCyd) prevented the dose dependent increase of SCE caused by BrdUrd. Cell growth inhibition produced by amino acid deprivation resulted in a significant increase in SCE as compared to exponentially growing cultures. This SCE enhancement was reduced by dCyd in HFC and did not occur in mouse 3T6 clone deficient in deoxycytidine deaminase. The modulation of SCE by DNA precursors is consistent with the induction of BrdUrd mutagenesis in mammalian cells and raises the possibility that common DNA changes are responsible for the induction of SCE and mutation in mammalian cells.