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 human keratinocytes were analysed during two cell cycles with respect to their cell cycle stage at the time of irradiation using BrdUrd/Hoechst flow cytometry. Exponentially growing SCL-2-keratinocytes exposed to UV-B radiation showed a short delay in G1-phase exit and were blocked in the S and G2/M phases of the first cell cycle. UV-A wavelengths did not show any detectable effect on cell cycle progression. In contrast, 137Cs-irradiation of these cells induced a temporary G2 block only. Micronucleus frequency increased in gamma-irradiated cells as soon as the cells started to divide and reached a plateau when most of the cells had divided. Continuous treatment with caffeine starting immediately after 137Cs gamma-irradiation prevented accumulation of cells in G2 phase, but did not influence the frequency of micronuclei. In UV-B-irradiated keratinocytes, however, the damage-induced cell cycle perturbations were merely reduced by caffeine, but not eliminated. Compared 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 cycle kinetics and micronucleus induction indicate different mechanisms of DNA damage caused by UV-B- and gamma-irradiation that may be repaired through different pathways.
Weller
E M
EM
Institut für Strahlenhygiene, Bundesamt für Strahlenschutz, Germany.
Hain
J
J
Jung
T
T
Kinder
R
R
Köfferlein
M
M
Burkart
W
W
Nüsse
M
M
D002110:Caffeine / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects* / Q000528:radiation effects*; D002460:Cell Line; D004249:DNA Damage; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays / Q000009:adverse effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000528:radiation effects*; D007700:Kinetics; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects* / Q000528:radiation effects*; D015162:Micronucleus Tests; D008938:Mitosis / Q000187:drug effects / Q000528:radiation effects; D016196:S Phase / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects*
D002110:Caffeine