A two-mutation model of radiation-induced acute myeloid leukemia using historical mouse data

Fieke Dekkers*, Harmen Bijwaard, Simon Bouffler, Michele Ellender, René Huiskamp, Christine Kowalczuk, Emmy Meijne, Marjolein Sutmuller

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

From studies of the atomic bomb survivors, it is well known that ionizing radiation causes several forms of leukemia. However, since the specific mechanism behind this process remains largely unknown, it is difficult to extrapolate carcinogenic effects at acute high-dose exposures to risk estimates for the chronic low-dose exposures that are important for radiation protection purposes. Recently, it has become clear that the induction of acute myeloid leukemia (AML) in CBA/H mice takes place through two key steps, both involving the Sfpi1 gene. A similar mechanism may play a role in human radiation-induced AML. In the present paper, a two-mutation carcinogenesis model is applied to model AML in several data sets of X-ray- and neutron-exposed CBA/H mice. The models obtained provide good fits to the data. A comparison between the predictions for neutron-induced and X-ray-induced AML yields an RBE for neutrons of approximately 3. The model used is considered to be a first step toward a model for human radiation-induced AML, which could be used to estimate risks of exposure to low doses.

Original languageEnglish
Pages (from-to)37-45
Number of pages9
JournalRadiation and Environmental Biophysics
Volume50
Issue number1
DOIs
Publication statusPublished - Mar 2011

Bibliographical note

Funding Information:
Acknowledgments The authors wish to thank Georg Gerber and the European Radiobiology Archive for providing the ENEA data. This study was supported financially by the European Union under contract FI6R-CT-2003-508842.

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