Wyld, L., Reed, M.W.R. and Brown, N.J. orcid.org/0000-0002-2100-1905 (1998) The influence of hypoxia and pH on aminolaevulinic acid-induced photodynamic therapy in bladder cancer cells in vitro. British Journal of Cancer, 77 (10). pp. 1621-1627. ISSN 0007-0920
Abstract
Photodynamic therapy (PDT) is a cancer treatment based on the interaction of light and a photosensitizing chemical. The photosensitizer protoporphyrin IX (PpIX) is generated via the haem biosynthetic pathway after administration of aminolaevulinic acid (ALA). The cellular microenvironment of tumours is hypoxic and acidotic relative to normal tissue, which may influence PpIX generation and compromise PDT efficacy. This study used bladder cancer cells, incubated with ALA at various oxygen tensions and H+ ion concentrations, and assessed the effects on PpIX generation and PDT sensitivity. PpIX production was reduced at 0%, 2.5% (19 mmHg) and 5% (38 mmHg) oxygen compared with that at 21% (160 mmHg) oxygen (0.15, 0.28 and 0.398 ng microg(-1) protein compared with 0.68 ng microg(-1) respectively; P < 0.05). The response to PDT was abolished by hypoxia, as a result of both reduced PpIX synthesis and reduced PDT toxicity. PpIX production was greater at pH 7.0 and 6.5 (0.75 and 0.66 ng microg(-1)) compared with that at pH 7.4 and 5.5 (0.41 and 0.55 ng microg(-1) respectively). PDT cytotoxicity was enhanced at lower pH values. These results suggest that ALA-induced PDT may be inhibited by hypoxia due to reduced intrinsic PpIX synthesis. Acidosis may slightly enhance the efficacy of ALA-induced PDT.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 1998 Cancer Research Campaign. This paper 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: | hypoxia; pH; aminolaevulinic acid; photodynamic therapy; 5-aminolevulinic acid; oxygen dependence; tumor; inactivation; 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 15:03 |
Last Modified: | 13 Dec 2016 15:09 |
Published Version: | http://dx.doi.org/10.1038/bjc.1998.265 |
Status: | Published |
Publisher: | Cancer Research UK |
Refereed: | Yes |
Identification Number: | 10.1038/bjc.1998.265 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:107788 |