Plasminogen activator: Induction of synthesis by DNA damage

Abstract

We have studied plasminogen activator (PA) synthesis in fibroblast cultures exposed to ultraviolet light (UV) and to several agents that produce DNA damage. PA synthesis was induced by UV in chicken, hamster, rat, mouse and human fibroblasts. The rate of enzyme synthesis, like the inhibition of 3H-thymidine incorporation, was a first-order function of UV fluence, and the UV sensitivity of these responses was very similar. The kinetics of PA induction after UV were much slower and the duration of synthesis much longer than following brief exposure to other inducing agents such as hormones, retinoids, tumor promoters or transforming viral genes; the ultimate level of PA production was in the same range as that induced by tumor promoters or viral transformation. PA synthesis was also induced by other agents that produce DNA damage. Those tested were neocarzinostatin, N-acetoxy-2-acetylaminofluorene, arabinosyl cytosine, mitomycin C and methyl methanesulfonate, some of which induce DNA repair of the “long” and others of the “short” type. These effects were not due merely to inhibition of DNA synthesis since they did not occur in cultures exposed to 5-fluoro-2′-deoxyuridine, 5-bromo-2′-deoxyuridine or methotrexate. Chick myotubes are post-mitotic cells in which DNA replication is permanently repressed, and they did not synthesize PA following exposure to DNA-damaging agents or UV. We discuss the potential relationship of PA production to post-irradiation inflammation and to the induction of DNA repair functions of the “SOS” type.