Only complete rejoining of DNA strand breaks after UVC allows K562 cell proliferation and DMSO induction of erythropoiesis.
DNA strand breaks are early intermediates of the repair of UVC-induced DNA damage, however, since they severely impair cellular activities, their presence should be limited in time. In this study, the effects of incomplete repair of UVC-induced DNA strand breaks are investigated on K562 cell growth and the induction of erythroid differentiation by addition of DMSO to the cell culture medium. The kinetics were followed after UV irradiation by single cell gel electrophoresis, and in total cell population by alkaline or neutral agarose gel electrophoresis. Shortly after exposure, an extensive fragmentation occurred in DNA; DNA double strand breaks were negatively correlated with recovery time for DNA integrity. DNA damage induced by UVC 9J/m2 rapidly triggered necrosis in a large fraction of irradiated K562 cells, and only 40% of treated cells resumed growth at a very low rate within 24h of culture. The addition of DMSO to the culture medium of cells 15min after UVC, when DNA strand break repair was not yet complete, produced apoptosis in >70% of surviving cells, as determined by TUNEL assay. Conversely, if DMSO was added when the resealing of DNA strand breaks was complete, surviving K562 cells retained full growth capacity, and their progeny underwent erythroid differentiation with normal levels of erythroid proteins, delta-aminolevulinic acid dehydrase and hemoglobin. This study shows that the extent of DNA strand break repair influences cell proliferation and the DMSO induced erythroid program, and the same UVC dose can have opposite effects depending on cellular status.
Foresti
Magda
M
University of Naples Federico II, Department of Biological Sciences, Section of Genetics and Molecular Biology, via Mezzocannone 8, 80134 Naples, Italy. magda.foresti@unina.it
Avallone
Bice
B
D015415:Biomarkers; D049109:Cell Proliferation / Q000528:radiation effects; D053960:DNA Breaks / Q000528:radiation effects*; D004260:DNA Repair; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004920:Erythropoiesis / Q000187:drug effects* / Q000528:radiation effects*; D006801:Humans; D020014:K562 Cells; D007700:Kinetics; D014466:Ultraviolet Rays
D015415:Biomarkers; D004121:Dimethyl Sulfoxide