Changes in gene expression by 193- and 248-nm excimer laser radiation in cultured human fibroblasts.
Tissue ablation by ultraviolet excimer lasers results in exposure of viable cells to subablative doses of radiation. To understand the potential biological consequences better, we have studied changes in gene expression in cultured human skin fibroblasts exposed to either 193- or 248-nm laser light. Northern blot analyses revealed that both treatments up-regulate a common set of genes, including interstitial collagenase, tissue inhibitor of metalloprotease, metallothionein, and the proto-oncogene c-fos. Dose-response and kinetic studies of collagenase induction by 193-nm radiation showed a maximal effect with 60 J/m2 and at approximately 24 h. The induction was still persistent 96 h later. In addition to the commonly affected genes, known to be activated also by conventional UV light (254 nm) and tumor-promoting phorbol esters, other genes were found to be selectively induced by the 193-nm radiation. The heat-shock hsp70 mRNA, undetectable in controls and in cultures irradiated at 248 nm, was transiently induced 8 h after exposure to 193-nm radiation. Furthermore, a selective up-regulation of collagen type I expression was observed. The results indicate that the 193- and 248-nm radiations by excimer lasers elicit specific and different cellular responses, in addition to an overlapping pathway of gene activation common also to UV radiation by germicidal lamps. The laser-induced genes could serve as molecular markers in evaluating cell injury in situ.
Rimoldi
D
D
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
Flessate
D M
DM
Samid
D
D
D017364:Collagenases / Q000378:metabolism; D005347:Fibroblasts / Q000528:radiation effects; D015870:Gene Expression / Q000528:radiation effects*; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007834:Lasers; D008668:Metallothionein / Q000378:metabolism; D003012:Microbial Collagenase / Q000037:antagonists & inhibitors; D000090063:Proto-Oncogene Mas; D019714:Tissue Inhibitor of Metalloproteinases; D014466:Ultraviolet Rays
D006023:Glycoproteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019714:Tissue Inhibitor of Metalloproteinases; D008668:Metallothionein; D017364:Collagenases; D003012:Microbial Collagenase