Mutagen-induced cell cycle delays are mediated through nucleotide pool imbalances

Exposure of mammalian cells to mutagenic agents causes delays in cell cycle progression. Such exposures also alter cellular deoxynucleotide triphosphate concentrations. The ratio of dTTP to dCTP increases rapidly after exposure to alkylating agents. To investigate whether these changes in nucleotide pool concentrations account for the induced cell cycle delay, Chinese hamster ovary (CHO) cells were exposed to either 30 of Gy X ray or different doses of methyl methanesulfonate (MMS) and then grown in the presence of 200 μM deoxycytidine for 24-48 hr. Deoxycytidine, which balances nucleotide pools, reversed some of the delay induced by X rays and MMS. In addition, the frequency of sister chromatid exchanges (SCE) in cells exposed to MMS followed by deoxycytidine was significantly higher than the frequency of SCEs in cells exposed to MMS alone. Presumably, reversing the cell cycle delay allows cells less time to repair damage that later leads to SCE formation. A similar response was found in human peripheral blood lymphocytes. Therefore, mutagen-induced cell cycle delays are mediated, at least in part, through nucleotide pool imbalances