Radiation leukaemogenesis at low doses DE-FG02-05 ER 63947 Final Technical Report 15 May 2005 14 May 2010

Bouffler, Simon¹  Badie, Christophe¹  Brown, Natalie¹  Finnon, Rosemary² 

[1] Health Protection Agency, Chilton (United Kingdom);Health Protection Agency,

关键词: DOSE-RESPONSE RELATIONSHIPS;    GENE MUTATIONS;    GENES;    GENETICS;    INDUCTION;    MUTATIONS;    RADIATIONS;    TESTING Radiation;    Leukaemia;    Mouse;    Sfpi1/PU.1;   

DOI  :  10.2172/984080
RP-ID  :  DOE/ER63947--1
PID  :  OSTI ID: 984080
Others  :  TRN: US1203432

美国|英语

来源: SciTech Connect

【 摘 要 】

This report provides a full summary of the results obtained under grant DE-FG02-05ER63947, Radiation Leukaemogenesis at low doses. The studies employed an experimental model of radiation leukaemogenesis with the main aim of identifying key events that convert normal cells into leukaemic cells follwoing exposure to radiation. Important aspect of the work was to understand dose-response relationships and time course relationships for leakaemogenis events. The studies performed provided evidence for direct radiation-induced losses of the Sfpi1/PU.1 gene being critical for induction of the disease. No threshold below 0.1 Gy in the induction of the gene losses was observed. The critical cell type in which the myeloid lekaemias arise has been identified and point mutations in the Sfpi1/PU.1 gene are common in leukaemias. The consequences of the genetic losses and mutation have been examined and these provide evidence of a disruption of differentiation in leukaemic cells. Additional pathways to leukaemogenesis have been identified also. Overall the study provides quantitiative data suitable for testing approaches to modelling of leukaemia rosk at low doses.