Induction of plasminogen activator by UV light in normal and xeroderma pigmentosum fibroblasts.

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Abstract
Normal and DNA repair-deficient human fibroblasts have been used to study induction of plasminogen activator (PA) by DNA damage. UV light induced the synthesis of PA in skin fibroblasts of all types of xeroderma pigmentosum (XP) in XP heterozygotes and in human amniotic cells. Enzyme induction was not observed in fibroblasts of normal adults. In classical XP, which are deficient in excision repair, PA synthesis occurred in a narrow range of low-UV fluences. In such strains, the level of enzyme produced was correlated with the extent of repair deficiency. UV fluences required for PA induction in XP variants and XP heterozygotes were at least 10 times those inducing enzyme synthesis in excision-deficient XP. Maximum enzyme induction occurred 48 h after irradiation and the highest levels of enzyme produced were 15-20 times those of PA baseline levels. Electrophoretic analysis showed that UV irradiation enhanced the synthesis of the MW 60,000 human urokinase-type PA, which is present in low amounts in untreated cells. PA induction in human cells is apparently caused by unrepaired DNA damage and represents a eukaryotic SOS-like function. PA induction may provide a sensitive assay for detection of cellular DNA repair deficiencies and identification of XP heterozygotes.