Miskin R, Ben-Ishai R
Proc Natl Acad Sci U S A. 1981 Oct;78(10):6236-40. doi: 10.1073/pnas.78.10.6236.
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, however, 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 hr after irradiation, and the highest levels of enzyme produced were 15-20 times those of PA baseline levels. Electrophoretic analysis showed that UV irradiation enhances the synthesis of the Mr 60,000 human urokinase-type PA, which is present in low amounts in untreated cells. Our results suggest that PA induction in human cells is caused by unrepaired DNA damage and represents a eukaryotic SOS-like function. In addition, PA induction may provide a sensitive assay for detection of cellular DNA repair deficiencies and identification of XP heterozygotes.
正常的和缺乏DNA修复能力的人成纤维细胞已被用于研究DNA损伤对纤溶酶原激活剂（PA）的诱导作用。紫外线可诱导所有类型的着色性干皮病（XP）的皮肤成纤维细胞、XP杂合子以及人羊膜细胞中PA的合成。然而，在正常成年人的成纤维细胞中未观察到酶的诱导现象。在缺乏切除修复能力的典型XP中，PA合成发生在低紫外线通量的狭窄范围内。在这类细胞系中，产生的酶水平与修复缺陷程度相关。XP变异型和XP杂合子中诱导PA所需的紫外线通量至少是在缺乏切除修复能力的XP中诱导酶合成所需通量的10倍。最大酶诱导作用在照射后48小时出现，产生的最高酶水平是PA基线水平的15 - 20倍。电泳分析表明，紫外线照射可增强60,000道尔顿的人尿激酶型PA的合成，该酶在未处理细胞中含量较低。我们的结果表明，人细胞中PA的诱导是由未修复的DNA损伤引起，并代表一种真核生物类似SOS的功能。此外，PA诱导可能为检测细胞DNA修复缺陷和鉴定XP杂合子提供一种灵敏的检测方法。
