Low-Dose Irradiation of Nontransformed Cells Stimulates the Selective Removal of Precancerous Cells via Intercellular Induction of Apoptosis
2007; American Association for Cancer Research; Volume: 67; Issue: 3 Linguagem: Inglês
10.1158/0008-5472.can-06-2985
ISSN1538-7445
AutoresDaniel I. Portess, Georg Bauer, Mark A. Hill, Peter O’Neill,
Tópico(s)Cancer Research and Treatments
ResumoAbstract 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) α-particles or low-LET γ-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 γ-rays and 0.29-mGy α-particles were sufficient to produce an observable increase in transformed cell apoptosis. This radiation-stimulated effect saturates at very low doses (50 mGy for γ-rays and 25 mGy for α-particles). The use of transforming growth factor-β (TGF-β) 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]
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