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Model of accelerated carcinogenesis based on proliferative stress and inflammation for doses relevant to radiotherapy

Schneider, Uwe; Schäfer, Brigitte (2012). Model of accelerated carcinogenesis based on proliferative stress and inflammation for doses relevant to radiotherapy. Radiation and Environmental Biophysics, 51(4):451-456.

Abstract

Recent findings demonstrate that accelerated carcinogenesis following liver regeneration is associated with chronic inflammation-induced double-strand DNA breaks in cells, which escaped apoptosis due to proliferative stress. In this work, proliferative stress and inflammation-based carcinogenesis at large dose were included in a cancer induction model considering fractionation. At large dose, tissue injury due to irradiation could be so severe that under the regenerative proliferative stress induced by cell loss, the genomic unstable cells generated during irradiation and/or inflammation escape senescence or apoptosis and reenter the cell cycle, triggering enhanced carcinogenesis. This acceleration—modeled to be proportional to the number of repopulated cells—is only significant, however, when tissue injury is severe and thus proportional to the cell loss in the tissue. The general solutions to the resulting differential equations for carcinoma induction were computed. In case of full repopulation or acute low-dose irradiation, the acceleration term disappears from the equation describing cancer induction. The acceleration term is affecting the dose-response curve for carcinogenesis only at large doses. An example for bladder cancer is shown. An existing model for cancer induction after fractionated radiotherapy which is based on cell mutations was extended here by including the effects of inflammation and proliferative stress, and an additional model parameter was established which describes acceleration. The new acceleration parameter affects the dose-response model only at large dose and is only effective when the tissue is not capable of fully repopulating between dose fractions

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:National licences > 142-005
Dewey Decimal Classification:Unspecified
Scopus Subject Areas:Life Sciences > Biophysics
Physical Sciences > Radiation
Physical Sciences > General Environmental Science
Language:English
Date:1 November 2012
Deposited On:21 Dec 2018 16:50
Last Modified:19 Oct 2024 01:42
Publisher:Springer
ISSN:0301-634X
OA Status:Green
Publisher DOI:https://doi.org/10.1007/s00411-012-0433-x
PubMed ID:22899337
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  • Content: Published Version
  • Language: English
  • Description: Nationallizenz 142-005

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