This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Portess, D. I. Articles by O'Neill, P. Search for Related Content PubMed PubMed Citation Articles by Portess, D. I. Articles by O'Neill, P.

Low-Dose Irradiation of Nontransformed Cells Stimulates the Selective Removal of Precancerous Cells via Intercellular Induction of Apoptosis

¹ Medical Research Council Radiation and Genome Stability Unit, Harwell, Didcot, Oxfordshire, United Kingdom and ² Abteilung Virologie, Institut fur Medizinische Mikrobiologie und Hygiene, Universität Freiburg, Freiburg, Germany

Requests for reprints: Peter O'Neill, Medical Research Council Radiation and Genome Stability Unit, Harwell, Didcot, OX11 0RD Oxfordshire, United Kingdom. Phone: 44-0-1235-841-000; Fax: 44-0-1235-841-200; E-mail: p.oneill{at}har.mrc.ac.uk.

An important stage in tumorigenesis is the ability of a precancerous cell to escape natural anticancer signals imposed on it by neighboring cells and its microenvironment. We have previously characterized a system of intercellular induction of apoptosis whereby nontransformed cells selectively remove transformed cells from coculture via cytokine and reactive oxygen/nitrogen species (ROS/RNS) signaling. We report that irradiation of nontransformed cells with low doses of either high linear energy transfer (LET) -particles or low-LET -rays leads to stimulation of intercellular induction of apoptosis. The use of scavengers and inhibitors confirms the involvement of ROS/RNS signaling and of the importance of transformed cell NADPH oxidase in the selectivity of the system. Doses as low as 2-mGy -rays and 0.29-mGy -particles were sufficient to produce an observable increase in transformed cell apoptosis. This radiation-stimulated effect saturates at very low doses (50 mGy for -rays and 25 mGy for -particles). The use of transforming growth factor-ß (TGF-ß) neutralizing antibody confirms a role for the cytokine in the radiation-induced signaling. The system may represent a natural anticancer mechanism stimulated by extremely low doses of ionizing radiation. [Cancer Res 2007;67(3):1246–53]

This article has been cited by other articles:

				M. Tubiana, L. E. Feinendegen, C. Yang, and J. M. Kaminski The Linear No-Threshold Relationship Is Inconsistent with Radiation Biologic and Experimental Data Radiology, April 1, 2009; 251(1): 13 - 22. [Full Text] [PDF]

				P WARDMAN The importance of radiation chemistry to radiation and free radical biology (The 2008 Silvanus Thompson Memorial Lecture) Br. J. Radiol., February 1, 2009; 82(974): 89 - 104. [Abstract] [Full Text] [PDF]

				C. A. Maxwell, M. C. Fleisch, S. V. Costes, A. C. Erickson, A. Boissiere, R. Gupta, S. A. Ravani, B. Parvin, and M. H. Barcellos-Hoff Targeted and Nontargeted Effects of Ionizing Radiation That Impact Genomic Instability Cancer Res., October 15, 2008; 68(20): 8304 - 8311. [Abstract] [Full Text] [PDF]