Berlin 2015 – wissenschaftliches Programm
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BP: Fachverband Biologische Physik
BP 15: Posters: Multi-cellular systems
BP 15.10: Poster
Montag, 16. März 2015, 17:30–19:30, Poster A
Mechanistic models of carcinogenesis: Radiation-induced risk of lung cancer in the Mayak workers — •Sascha Zöllner1, Mikhail Sokolnikov2, and Markus Eidemüller1 — 1Helmholtz Zentrum München, Institute of Radiation Protection (Germany) — 2Southern Urals Biophysics Institute, Ozyorsk (Russia)
Mechanistic multi-stage models are used to analyze lung-cancer mortality after Plutonium exposure in the Mayak-workers cohort. Besides the established two-stage model with clonal expansion, models with three mutation stages as well as a model with two distinct pathways to cancer are studied. The results suggest that three-stage models offer an improved description of the data. The best-fitting models point to a mechanism where radiation increases the rate of clonal expansion. This is interpreted in terms of changes in cell-cycle control mediated by bystander signaling or repopulation following cell killing. To elucidate the implications of the different models for radiation risk, several exposure scenarios are studied. Models with a radiation effect at an early stage show a delayed response and a pronounced drop-off with older ages at exposure. Moreover, the dose-response relationship is strongly nonlinear, revealing a marked increase above a critical dose.