BJR
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
First published online April 14, 2009
British Journal of Radiology (2009) 82, 847-854
© 2009 British Institute of Radiology
doi: 10.1259/bjr/35746067
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by ANOOPKUMAR-DUKIE, S
Right arrow Articles by ALLSHIRE, A
PubMed
Right arrow PubMed Citation
Right arrow Articles by ANOOPKUMAR-DUKIE, S
Right arrow Articles by ALLSHIRE, A

Mitochondrial modulation of oxygen-dependent radiosensitivity in some human tumour cell lines

S ANOOPKUMAR-DUKIE, PhD 1,3 T CONERE, PhD 2 G D SISK, BSc 1 and A ALLSHIRE, PhD 1

1 Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland, 2 Department of Medical Physics, Cork University Hospital, Wilton, Cork, Ireland and 3 School of Pharmacy, Gold Coast Campus, Griffith University, Queensland 4222, Australia

Correspondence: Dr Ashley Allshire, Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland. E-mail: a.allshire{at}ucc.ie

Oxygen-dependent radiosensitivity of tumour cells reflects direct oxidative damage to DNA, but non-nuclear mechanisms including signalling pathways may also contribute. Mitochondria are likely candidates because not only do they integrate signals from each of the main kinase pathways but mitochondrial kinases responsive to oxidative stress communicate to the rest of the cell. Using pharmacological and immunochemical methods, we tested the role of mitochondrial permeability transition (MPT) and the Bcl-2 proteins in oxygen-dependent radiosensitivity. Drug-treated or untreated cervical cancer HeLa, breast cancer MCF-7 and melanoma MeWo cell lines were irradiated at 6.2 Gy under normoxic and hypoxic conditions then allowed to proliferate for 7 days. The MPT blocker cyclosporin A (2 µM) strongly protected HeLa but not the other two lines against oxygen-dependent radiosensitivity. By contrast, bongkrekic acid (50 µM), which blocks MPT by targeting the adenine nucleotide transporter, had only marginal effect and calcineurin inhibitor FK-506 (0.1 µM) had none. Nor was evidence found for the modulation of oxygen-dependent radiosensitivity by Bax/Bcl-2 signalling, mitochondrial ATP-dependent potassium (mitoKATP) channels or mitochondrial Ca2+ uptake. In conclusion, calcineurin-independent protection by cyclosporin A suggests that MPT but not mitoKATP or the mitochondrial apoptosis pathway plays a causal role in oxygen-dependent radiosensitivity of HeLa cells. Targeting MPT may therefore improve the effectiveness of radiotherapy in some solid tumours.






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
BJR DMFR IMAGING  ALL BIR JOURNALS 
Copyright © 2009 by the British Institute of Radiology.