title: A two-mutation model of radiation-induced acute myeloid leukemia using historical mouse data.
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.
authors.affiliation: Laboratory of Radiation Research, Bilthoven, The Netherlands. fieke.dekkers@rivm.nl
authors.forename: Fieke
authors.initials: F
authors.lastname: Dekkers
authors.forename: Harmen
authors.initials: H
authors.lastname: Bijwaard
authors.forename: Simon
authors.initials: S
authors.lastname: Bouffler
authors.forename: Michele
authors.initials: M
authors.lastname: Ellender
authors.forename: René
authors.initials: R
authors.lastname: Huiskamp
authors.forename: Christine
authors.initials: C
authors.lastname: Kowalczuk
authors.forename: Emmy
authors.initials: E
authors.lastname: Meijne
authors.forename: Marjolein
authors.initials: M
authors.lastname: Sutmuller
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D015470:Leukemia, Myeloid, Acute / Q000209:etiology / Q000235:genetics*; D016013:Likelihood Functions; D008297:Male; D051379:Mice; D008954:Models, Biological; D009154:Mutation / Q000528:radiation effects*; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D009502:Neutrons / Q000009:adverse effects; D012062:Relative Biological Effectiveness; D013269:Stochastic Processes