PuSH - Publication Server of Helmholtz Zentrum München: Mechanistic modeling predicts anti-carcinogenic radiation effects on intercellular signaling in vitro turn pro-carcinogenic in vivo.

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Kundrat, P. ; Friedland, W.

Mechanistic modeling predicts anti-carcinogenic radiation effects on intercellular signaling in vitro turn pro-carcinogenic in vivo.

Radiat. Prot. Dosim. 183, 223-227 (2019)

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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.

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