Caffeine induces sister-chromatid exchanges during the whole S-phase of the cell cycle.

The capacity of caffeine to induce sister chromatid exchanges (SCEs) in different cell cycle stages and the proliferation kinetics were studied. Continuous treatment with this xanthine during the whole second cycle significantly increased the baseline SCE frequency. Pulse-treatment experiments showed that the induction of SCEs by caffeine, which was dose-dependent, was restricted to the S-phase of the cell cycle without effect on G1 or G2 cells. Moreover, unlike other SCE-inducing agents, such as DNA-synthesis inhibitors and DNA-damaging agents, caffeine produced similar SCE increases in cells treated at different times throughout the S-phase. In the light of Painter's model for SCE formation and the known effects of caffeine on the DNA replication pattern, the most likely mechanism of SCE induction by caffeine is an increase in the number of DNA-replication sites.