Low-dose irradiation of nontransformed cells stimulates the selective removal of precancerous cells via intercellular induction of apoptosis.
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) alpha-particles or low-LET gamma-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 gamma-rays and 0.29-mGy alpha-particles were sufficient to produce an observable increase in transformed cell apoptosis. This radiation-stimulated effect saturates at very low doses (50 mGy for gamma-rays and 25 mGy for alpha-particles). The use of transforming growth factor-beta (TGF-beta) 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.
Portess
Daniel I
DI
Medical Research Council Radiation and Genome Stability Unit, Harwell, Didcot, Oxfordshire, UK.
Bauer
Georg
G
Hill
Mark A
MA
O'Neill
Peter
P
D000512:Alpha Particles; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects*; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000473:pathology / Q000528:radiation effects; D005720:Gamma Rays; D019255:NADPH Oxidases / Q000378:metabolism; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D051381:Rats; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000528:radiation effects; D016212:Transforming Growth Factor beta / Q000276:immunology
D000906:Antibodies; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D019255:NADPH Oxidases