RRC ID 37683
著者 Ban N, Kai M.
タイトル Implication of replicative stress-related stem cell ageing in radiation-induced murine leukaemia.
ジャーナル Br J Cancer
Abstract BACKGROUND:The essential aetiology of radiation-induced acute myeloid leukaemia (AML) in mice is the downregulation of the transcription factor PU.1. The causative mutation of the PU.1-endocing Sfpi1 gene consists mostly of C:G to T:A transitions at a CpG site and is likely to be of spontaneous origin. To work out a mechanism underlying the association between radiation exposure and the AML induction, we have hypothesised that replicative stress after irradiation accelerates the ageing of haematopoietic stem cells (HSCs), and the ageing-related decline in DNA repair could affect the spontaneous mutation rates.
METHODS:Mathematical model analysis was conducted to examine whether and to what extent the cell kinetics of HSCs can be modified after irradiation. The haematopoietic differentiation process is expressed as a mathematical model and the cell-kinetics parameters were estimated by fitting the simulation result to the assay data.
RESULTS:The analysis revealed that HSCs cycle vigourously for more than a few months after irradiation. The estimated number of cell divisions per surviving HSC in 3 Gy-exposed mice reached as high as ten times that of the unexposed.
INTERPRETATION:The mitotic load after 3 Gy irradiation seems to be heavy enough to accelerate the ageing of HSCs and the hypothesis reasonably explains the leukaemogenic process.
巻・号 101(2)
ページ 363-71
公開日 2009-7-21
DOI 10.1038/sj.bjc.6605135
PII 6605135
PMID 19513063
PMC PMC2720201
MeSH Acute Disease Animals Cell Division / physiology Cell Division / radiation effects* Cellular Senescence / physiology Cellular Senescence / radiation effects* Hematopoietic Stem Cells / pathology* Leukemia, Myeloid / etiology Leukemia, Myeloid / pathology* Leukemia, Radiation-Induced / pathology* Male Mice Mice, Inbred C3H Mitosis / physiology Mitosis / radiation effects Models, Biological
IF 5.791
引用数 17
WOS 分野 ONCOLOGY
リソース情報
ヒト・動物細胞 MC3T3-G2/PA6(RCB1127)