論文 - 詳細
RRC ID | 37683 |
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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) |