Induction of sister chromatid exchanges by 5-fluorodeoxycytidine: correlation with DNA methylation

Chinese hamster ovary cells grown in medium containing 10 microM 5-fluorodeoxycytidine for forty-eight hours were found to have up to 5% of the deoxycytidine residues of the DNA substituted by this analog. Cytological studies of these cells showed that the incorporated 5-FdC caused a two-fold increase of sister chromatid exchanges (SCE) over the control level. However, 5-FdC was capable of inducing SCE only after it had been present in the cell for at least two cycles of DNA synthesis. This is in contrast to several other chemicals that we have tested which induced SCE immediately after the first DNA synthesis. We consider the possibility that the delayed effect may be related to hypomethylation of cytosine in the newly replicated DNA.