Beyond two-stage models for lung carcinogenesis in the Mayak workers: implications for plutonium risk.
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...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4441484?pdf=render |
| _version_ | 1818215194959020032 |
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| author | Sascha Zöllner Mikhail E Sokolnikov Markus Eidemüller |
| author_facet | Sascha Zöllner Mikhail E Sokolnikov Markus Eidemüller |
| author_sort | Sascha Zöllner |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T06:32:13Z |
| format | Article |
| id | doaj.art-bd83b6a68a7949298332cdc1e602e36a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T06:32:13Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-bd83b6a68a7949298332cdc1e602e36a2022-12-22T00:34:33ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01105e012623810.1371/journal.pone.0126238Beyond two-stage models for lung carcinogenesis in the Mayak workers: implications for plutonium risk.Sascha ZöllnerMikhail E SokolnikovMarkus EidemüllerMechanistic 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.http://europepmc.org/articles/PMC4441484?pdf=render |
| spellingShingle | Sascha Zöllner Mikhail E Sokolnikov Markus Eidemüller Beyond two-stage models for lung carcinogenesis in the Mayak workers: implications for plutonium risk. PLoS ONE |
| title | Beyond two-stage models for lung carcinogenesis in the Mayak workers: implications for plutonium risk. |
| title_full | Beyond two-stage models for lung carcinogenesis in the Mayak workers: implications for plutonium risk. |
| title_fullStr | Beyond two-stage models for lung carcinogenesis in the Mayak workers: implications for plutonium risk. |
| title_full_unstemmed | Beyond two-stage models for lung carcinogenesis in the Mayak workers: implications for plutonium risk. |
| title_short | Beyond two-stage models for lung carcinogenesis in the Mayak workers: implications for plutonium risk. |
| title_sort | beyond two stage models for lung carcinogenesis in the mayak workers implications for plutonium risk |
| url | http://europepmc.org/articles/PMC4441484?pdf=render |
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