Abstract |
Mechanistic multi-stage models are used to analyze lung-cancer mortality after Plutonium exposure in the Mayak-workers cohort, with follow-up until 2008. 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. No statistical evidence for a two-pathway model is found. 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 for all three-stage models, revealing a marked increase above a critical dose.
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Authors | Sascha Zöllner, Mikhail E Sokolnikov, Markus Eidemüller |
Journal | PloS one
(PLoS One)
Vol. 10
Issue 5
Pg. e0126238
( 2015)
ISSN: 1932-6203 [Electronic] United States |
PMID | 26000637
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Dose-Response Relationship, Radiation
- Humans
- Lung Neoplasms
(diagnosis, etiology, mortality)
- Middle Aged
- Models, Theoretical
- Neoplasms, Radiation-Induced
(diagnosis, mortality)
- Occupational Exposure
(adverse effects)
- Plutonium
(toxicity)
- Risk Factors
- Young Adult
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