CAFFEINE INHIBITS GENE-SPECIFIC REPAIR OF UV-INDUCED DNA-DAMAGE IN HAMSTER-CELLS AND IN HUMAN XERODERMA-PIGMENTOSUM GROUP-C CELLS

We have studied the effect of caffeine on gene- and strand-specific DN A repair after exposure of Chinese hamster ovary cells and human xerod erma pigmentosum complementation group C (XPC) cells to ultraviolet ir radiation (UV). In hamster cells, caffeine inhibited the repair of cyc lobutane dimers (CPDs) in the dihydrofolate reductase (DHFR) gene by u p to 66% after 8 h of repair incubation. This effect was dose-dependen t, with more inhibition at 10 than at 1.5 mM caffeine. The inhibition was due to decreased repair in the transcribed strand of the hamster D HFR gene. This decrease in repair of CPDs in the DHFR gene correlated with an enhancement of UV-induced cell killing by caffeine. DNA repair was also measured in the overall genome by repair-replication analysi s. In hamster cells, caffeine caused a modest enhancement of repair. C affeine did not produce a significant effect on cell cycle progression up to 8 h after UV irradiation, but it caused a distinct block in ear ly S phase during the 24 h post-irradiation period. In XPC cells, 10 m M caffeine inhibited the removal of CPDs from the transcribed strand o f the DHFR gene by 92%. The removal of all photoproducts from the over all genome was inhibited by 26% in these cells. Since the residual rep air in XPC cells is thought to occur in active genomic regions, we pro pose that caffeine preferentially inhibits gene-specific repair.