DNA repair and induction of plasminogen activator in human fetal cells treated with ultraviolet light.
We have tested human fetal fibroblasts for development associated changes in DNA repair by utilizing nucleoid sedimentation as an assay for excision repair. Among skin fibroblasts the rate of excision repair was significantly higher in non-fetal cells than in fibroblasts derived from an 8 week fetus; this was evident by a delay in both the relaxation and the restoration of DNA supercoiling in nucleoids after irradiation. Skin fibroblasts derived at 12 week gestation were more repair proficient than those derived at 8 week gestation. However, they exhibited a somewhat lower rate of repair than non-fetal cells. The same fetal and non-fetal cells were also tested for induction of the protease plasminogen activator (PA) after u.v. irradiation. Enhancement of PA was higher in skin fibroblasts derived at 8 week than in those derived at 12 week gestation and was absent in non-fetal skin fibroblasts. These results are consistent with our previous findings that in human cells u.v. light-induced PA synthesis is correlated with reduced DNA repair capacity. Excision repair and PA inducibility were found to depend on tissue of origin in addition to gestational stage, as shown for skin and lung fibroblasts from the same 12 week fetus. Lung compared to skin fibroblasts exhibited lower repair rates and produced higher levels of PA after irradiation. The sedimentation velocity of nucleoids, prepared from unirradiated fibroblasts, in neutral sucrose gradients with or without ethidium bromide, indicated the presence of DNA strand breaks in fetal cells. It is proposed that reduced DNA repair in fetal cells may result from alterations in DNA supercoiling, and that persistent DNA strand breaks enhance transcription of PA gene(s).
D002460:Cell Line; D004260:DNA Repair / Q000528:radiation effects*; D004622:Embryo, Mammalian; D005260:Female; D005333:Fetus; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D007700:Kinetics; D008168:Lung / Q000196:embryology / Q000528:radiation effects; D010960:Plasminogen Activators / Q000096:biosynthesis*; D011247:Pregnancy; D012867:Skin / Q000196:embryology / Q000528:radiation effects; D014466:Ultraviolet Rays
D010960:Plasminogen Activators