title: Mapping of oxidative stress responses of human tumor cells following photodynamic therapy using hexaminolevulinate.
abstract: BACKGROUND
  Photodynamic therapy (PDT) involves systemic or topical administration of a lesion-localizing photosensitizer or its precursor, followed by irradiation of visible light to cause singlet oxygen-induced damage to the affected tissue. A number of mechanisms seem to be involved in the protective responses to PDT, including activation of transcription factors, heat shock proteins, antioxidant enzymes and apoptotic pathways.
  
  
  RESULTS
  In this study, we address the effects of a destructive/lethal hexaminolevulinate (HAL) mediated PDT dose on the transcriptome by using transcriptional exon evidence oligo microarrays. Here, we confirm deviations in the steady state expression levels of previously identified early defence response genes and extend this to include unreported PDT inducible gene groups, most notably the metallothioneins and histones. HAL-PDT mediated stress also altered expression of genes encoded by mitochondrial DNA (mtDNA). Further, we report PDT stress induced alternative splicing. Specifically, the ATF3 alternative isoform (deltaZip2) was up-regulated, while the full-length variant was not changed by the treatment. Results were independently verified by two different technological microarray platforms. Good microarray, RT-PCR and Western immunoblotting correlation for selected genes support these findings.
  
  
  CONCLUSIONS
  Here, we report new insights into how destructive/lethal PDT alters the transcriptome not only at the transcriptional level but also at post-transcriptional level via alternative splicing.
authors: Department of Tumor Biology, Rikshopitalet - Radiumhospitalet Medical Center, 0310 Oslo, Norway. linac@rr-research.no
authors: Lina
authors: L
authors: Cekaite
authors: Qian
authors: Q
authors: Peng
authors: Andrew
authors: A
authors: Reiner
authors: Susan
authors: S
authors: Shahzidi
authors: Siri
authors: S
authors: Tveito
authors: Ingegerd E
authors: IE
authors: Furre
authors: Eivind
authors: E
authors: Hovig
mesh_terms: D051700:Activating Transcription Factor 3 / Q000378:metabolism; D017398:Alternative Splicing / Q000187:drug effects; D000622:Aminolevulinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D005091:Exons; D005786:Gene Expression Regulation / Q000187:drug effects; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D045726:Metalloproteases / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: C490449:ATF3 protein, human; D051700:Activating Transcription Factor 3; D004272:DNA, Mitochondrial; D006657:Histones; D017319:Photosensitizing Agents; D020033:Protein Isoforms; D016271:Proto-Oncogene Proteins c-myc; D000622:Aminolevulinic Acid; D048670:MAP Kinase Kinase 4; D045726:Metalloproteases; C419924:5-aminolevulinic acid hexyl ester
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