Wyld, L., Smith, O., Lawry, J. et al. (2 more authors) (1998) Cell cycle phase influences tumour cell sensitivity to aminolaevulinic acid-induced photodynamic therapy in vitro. British Journal of Cancer, 78 (1). pp. 50-55. ISSN 0007-0920
Abstract
Photodynamic therapy (PDT) is a form of cancer treatment based on the destruction of cells by the interaction of light, oxygen and a photosensitizer. Aminolaevulinic acid (ALA) is the prodrug of the photosensitizer protoporphyrin IX (PpIX). ALA-induced PDT depends on the rate of cellular synthesis of PpIX, which may vary with cell cycle phase. This study has investigated the relationship between cell cycle phase, PpIX generation and phototoxicity in synchronized and unsynchronized bladder cancer cells (HT1197). In unsynchronized cells, relative PpIX fluorescence values (arbitrary units) were significantly different between cell cycle phases after a 1-h ALA incubation (G1 24.8 +/- 0.7; S-phase, 32.7 +/- 0.8, P < 0.05; G2 35.4 +/- 0.8, P < 0.05). In synchronized cells after a 1-h ALA incubation, cells in G1 produced less PpIX than those in S-phase or G2 [6.65 +/- 1.1 ng per 10(5) cells compared with 15.5 +/- 2.1 (P < 0.05), and 8.1 +/- 1.8 ng per 10(5) cells (not significant) respectively] and were significantly less sensitive to ALA-induced PDT (% survival, G1 76.2 +/- 8.3; S-phase 49.7 +/- 4.6, P < 0.05; G2 44.2 +/- 2.4, P < 0.05). This differential response in tumour cells may have implications for clinical PDT, resulting in treatment resistance and possible failure in complete tumour response.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 1998 Cancer Research UK. This article is 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: | cell cycle; aminolaevulinic acid; photodynamic therapy; in vitro; photoradiation; accumulation; kinetics; invitro; oxygen; ala |
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 10:08 |
Last Modified: | 13 Dec 2016 10:08 |
Published Version: | http://dx.doi.org/10.1038/bjc.1998.441 |
Status: | Published |
Publisher: | Cancer Research UK |
Refereed: | Yes |
Identification Number: | 10.1038/bjc.1998.441 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:107787 |