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Open Access Research article

Mapping of oxidative stress responses of human tumor cells following photodynamic therapy using hexaminolevulinate

Lina Cekaite1*, Qian Peng23, Andrew Reiner1, Susan Shahzidi2, Siri Tveito1, Ingegerd E Furre2 and Eivind Hovig1

Author Affiliations

1 Department of Tumor Biology, Rikshopitalet – Radiumhospitalet Medical Center, 0310 Oslo, Norway

2 Department of Pathology, Rikshopitalet – Radiumhospitalet Medical Center, 0310 Oslo, Norway

3 State Key Lab for Advanced Photonic Materials and Devices, Fudan University, Shanghai, P.R. China

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BMC Genomics 2007, 8:273  doi:10.1186/1471-2164-8-273

Published: 13 August 2007

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.

Conclusion

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.