Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

PNAS 101 (37): 13495-13500

Copyright © 2004 by the National Academy of Sciences.

CELL BIOLOGY

Targeted cytoplasmic irradiation induces bystander responses

Chunlin Shao, Melvyn Folkard, Barry D. Michael, and Kevin M. Prise *

Gray Cancer Institute, P.O. Box 100, Mount Vernon Hospital, Northwood, Middlesex HA6 2JR, United Kingdom

Edited by Richard B. Setlow, Brookhaven National Laboratory, Upton, NY, and approved August 4, 2004

Received for publication July 8, 2004.

Abstract: The observation of radiation-induced bystander responses, in which cells respond to their neighbors being irradiated, has important implications for understanding mechanisms of radiation action particularly after low-dose exposure. Much of this questions the current dogma of direct DNA damage driving response in irradiated systems. In this study, we have used a charged-particle microbeam to target individual helium ions (3He2+) to individual cells within a population of radioresistant glioma cells cultured alone or in coculture with primary human fibroblasts. We found that even when a single cell within the glioma population was precisely traversed through its cytoplasm with one 3He2+ ion, bystander responses were induced in the neighboring nonirradiated glioma or fibroblasts so that the yield of micronuclei was increased by 36% for the glioma population and 78% for the bystander fibroblast population. Importantly, the yield of bystander-induced micronuclei was independent of whether the cytoplasm or nucleus of a cell was targeted. The bystander responses were fully eliminated when the populations were treated with 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide or filipin, which scavenge nitric oxide (NO) and disrupt membrane rafts, respectively. By using the probe 4-amino-5-methylamino-2',7'-difluorofluorescein, it was found that the NO level in the glioma population was increased by 15% after 1 or 10 cytoplasmic traversals, and this NO production was inhibited by filipin. This finding shows that direct DNA damage is not required for switching on of important cell-signaling mechanisms after low-dose irradiation and that, under these conditions, the whole cell should be considered a sensor of radiation exposure.

This paper was submitted directly (Track II) to the PNAS office.

Abbreviations: NO, nitric oxide; MN, micronucleus; c-PTIO, 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide; GEMs, glycosphingolipid-enriched membrane microdomains.

* To whom correspondence should be addressed. E-mail: prise{at}gci.ac.uk.

© 2004 by The National Academy of Sciences of the USA

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Microbeams in radiation biology: review and critical comparison.
K. M. Prise and G. Schettino (2011)
Radiat Prot Dosimetry 143, 335-339
   Abstract »    Full Text »    PDF »
Exogenous carbon monoxide protects the bystander Chinese hamster ovary cells in mixed coculture system after alpha-particle irradiation.
W. Han, L. Wu, S. Chen, and K.N. Yu (2010)
Carcinogenesis 31, 275-280
   Abstract »    Full Text »    PDF »
ATM Acts Downstream of ATR in the DNA Damage Response Signaling of Bystander Cells.
S. Burdak-Rothkamm, K. Rothkamm, and K. M. Prise (2008)
Cancer Res. 68, 7059-7065
   Abstract »    Full Text »    PDF »
DNA Double-Strand Breaks after Percutaneous Transluminal Angioplasty.
D. Geisel, J. T. Heverhagen, M. Kalinowski, and H.-J. Wagner (2008)
Radiology 248, 852-859
   Abstract »    Full Text »    PDF »
Mitochondrial Function and Nuclear Factor-{kappa}B-Mediated Signaling in Radiation-Induced Bystander Effects.
H. Zhou, V. N. Ivanov, Y.-C. Lien, M. Davidson, and T. K. Hei (2008)
Cancer Res. 68, 2233-2240
   Abstract »    Full Text »    PDF »
Cytoplasmic Irradiation Induces Mitochondrial-Dependent 53BP1 Protein Relocalization in Irradiated and Bystander Cells.
L. Tartier, S. Gilchrist, S. Burdak-Rothkamm, M. Folkard, and K. M. Prise (2007)
Cancer Res. 67, 5872-5879
   Abstract »    Full Text »    PDF »
Targeted and Nontargeted Effects of Low-Dose Ionizing Radiation on Delayed Genomic Instability in Human Cells.
L. Huang, P. M. Kim, J. A. Nickoloff, and W. F. Morgan (2007)
Cancer Res. 67, 1099-1104
   Abstract »    Full Text »    PDF »
New advances in radiation biology.
K. M. Prise (2006)
Occup. Med. 56, 156-161
   Abstract »    Full Text »    PDF »
In vivo formation and repair of DNA double-strand breaks after computed tomography examinations.
M. Lobrich, N. Rief, M. Kuhne, M. Heckmann, J. Fleckenstein, C. Rube, and M. Uder (2005)
PNAS 102, 8984-8989
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882