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 strandspecificDNA repair after exposure of Chinese hamster ovary cells andhuman xeroderma pigmentosum complementation group C (XPC) cellsto ultraviolet irradiation (UV). In hamster cells, caffeineinhibited the repair of cyclobutane dimers (CPDs) in the dihydrofolatereductase (DHFR) gene by up to 66% after 8 h of repair incubation.This effect was dose-dependent, with more inhibition at 10 thanat 1.5 mM caffeine. The inhibition was due to decreased repairin the transcribed strand of the hamster DHFR gene. This decreasein repair of CPDs in the DHFR gene correlated with an enhancementof UV-induced cell killing by caffeine. DNA repair was alsomeasured in the overall genome by repair—replication analysis.In hamster cells, caffeine caused a modest enhancement of repair.caffeine did not produce a significant effect on cell cycleprogression up to 8 h after UV irradiation, but it caused adistinct block in early S phase during the 24 h post-irradiationperiod. In XPC cells, 10 mM caffeine inhibited the removal ofCPDs from the transcribed strand of the DHFR gene by 92% Theremoval of all Photoproducts from the overall genome was inhibitedby 26% in these cells. Since the residual repair in XPC cellsis thought to occur in active genomic regions, we propose thatcaffeine preferentially inhibits gene-specific repair.