Wyld, L., Burn, J.L., Reed, M.W.R. et al. (1 more author) (1997) Factors affecting amninolaevulinic acid-induced generation of protoporphyrin IX. British Journal of Cancer, 76 (6). pp. 705-712. ISSN 0007-0920
Abstract
Photodynamic therapy (PDT) may cause tumour cell destruction by direct toxicity or by inducing cellular hypoxia as a result of microcirculatory shutdown. Aminolaevulinic acid (ALA) causes cellular accumulation of protoporphyrin IX (PPIX) in cells exposed to it in excess. PPIX can be used as a photosensitizer for PDT. Microcirculatory shutdown may be induced by toxicity to the endothelial and vascular smooth muscle (VSM) cells or by release of vasoactive substances. We have studied whether PPIX is produced by endothelial, VSM and tumour cells on exposure to ALA and whether these cell lines are directly damaged by PDT in vitro. Tumour endothelial cells are angiogenic and we have, therefore, investigated the effect of cellular proliferation rates on PPIX generation. Tumour cells generate more PPIX intracellularly than the non-neoplastic cell lines studied and are correspondingly more sensitive to PDT-induced cytotoxicity. Endothelial cells are sensitive to PDT-induced cytotoxicity and accumulate between 1.5 and four times more PPIX when proliferating (as during tumour-induced angiogenesis) than when quiescent. We conclude that PPIX-mediated PDT may exert some of its effects on the microcirculation of treated tissues by direct toxicity to endothelial and VSM cells, and that this toxicity may be enhanced in the tumour microenvironment.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 1997 Cancer Research Campaign. This article is available under the terms of the Creative Commons Licence, Attribution-Non-Commercial-Share-Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/. |
Keywords: | photodynamic therapy; microcirculation; aminolaevulinic acid; protoporphyrin IX; endothelial cells; heme biosynthetic-pathway; photodynamic therapy; 5-aminolevulinic acid; porphyrin accumulation; endothelial-cells; ala; photodestruction; fluorescence; lymphocytes; invitro |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 13 Dec 2016 11:20 |
Last Modified: | 13 Dec 2016 11:20 |
Published Version: | http://dx.doi.org/10.1038/bjc.1997.450 |
Status: | Published |
Publisher: | Cancer Research UK |
Refereed: | Yes |
Identification Number: | 10.1038/bjc.1997.450 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:107790 |
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