UV-B-INDUCED CELL-CYCLE PERTURBATIONS, MICRONUCLEUS INDUCTION, AND MODULATION BY CAFFEINE IN HUMAN KERATINOCYTES

UV-B-induced perturbations of cell cycle progression in asynchronous h uman keratinocytes were analysed during two cell cycles with respect t o their cell cycle stage at the time of irradiation using BrdUrd/Hoech st flow Cytometry. Exponentially growing SCL-2-keratinocytes exposed t o UV-B radiation showed a short delay in Gi-phase exit and were blocke d in the S and G(2)/M phases of the first cell cycle. UV-A wavelengths did not show any detectable effect on cell cycle progression. In cont rast, Cs-137-irradiation of these cells induced a temporary G(2) block only. Micronucleus frequency increased in gamma-irradiated cells as s oon as the cells started to divide and reached a plateau when most of the cells had divided. Continuous treatment with caffeine starting imm ediately after Cs-137 gamma-irradiation prevented accumulation of cell s in G(2) phase, but did not influence the frequency of micronuclei. I n UV-B-irradiated keratinocytes, however, the damage-induced cell cycl e perturbations were merely reduced by caffeine, but not eliminated. C ompared with gamma-irradiation a moderate induction of micronuclei was observed in UV-B-irradiated cells. Caffeine, however, potentiated the induction of micronuclei by UV-B. These different effects on cell cyc le kinetics and micronucleus induction indicate different mechanisms o f DNA damage caused by UV-B- and gamma-irradiation that may be repaire d through different pathways.