1. MECHANISTIC MODELING PREDICTS ANTI-CARCINOGENIC RADIATION EFFECTS ON INTERCELLULAR SIGNALING IN VITRO TURN PRO-CARCINOGENIC IN VIVO.
- Author
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Kundrát P and Friedland W
- Subjects
- Apoptosis physiology, Cell Line, Transformed, Cell Transformation, Neoplastic pathology, Cytokines pharmacology, Humans, Models, Biological, Radiation, Ionizing, Reactive Oxygen Species pharmacology, Signal Transduction radiation effects, Anticarcinogenic Agents radiation effects, Apoptosis radiation effects, Cell Transformation, Neoplastic radiation effects, Neoplasms radiotherapy
- Abstract
Oncogenic transformed cells represent an in vitro system mimicking early-stage carcinogenesis. These precancerous cells are subject to a selective removal via apoptosis induced by neighbor cells. By modulating the underpinning intercellular signaling mediated by cytokines and reactive oxygen/nitrogen species, ionizing radiation enhances this removal of precancerous cells in vitro, at doses from a few mGy to a few Gy. However, epidemiological data demonstrate that radiation exposure induces cancer, at least above 100 mGy. Mechanistic modeling of the given anti-carcinogenic process explains this discrepancy: The model reproduces in vitro data on apoptosis and its enhancement by radiation. For in vivo-like conditions with signal lifetimes shorter and cell densities higher than in vitro, radiation is predicted to reduce this anti-carcinogenic mechanism. Early-stage lesions that would be turned dormant or completely removed may grow large and escape this control mechanism upon irradiation., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Published
- 2019
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