title: Radiation leukemogenesis in mice: loss of PU.1 on chromosome 2 in CBA and C57BL/6 mice after irradiation with 1 GeV/nucleon 56Fe ions, X rays or gamma rays. Part I. Experimental observations.
abstract: Since deletion of the PU.1 gene on chromosome 2 is a crucial acute myeloid leukemia (AML) initiating step in the mouse model, we quantified PU.1 deleted cells in the bone marrow of gamma-, X- and 56Fe-ion-irradiated mice at various times postirradiation. Although 56Fe ions were initially some two to three times more effective than X or gamma rays in inducing PU.1 deletions, by 1 month postirradiation, the proportions of cells with PU.1 deletions were similar for the HZE particles and the sparsely ionizing radiations. These results indicate that while 56Fe ions are more effective in inducing PU.1 deletions, they are also more effective in causing collateral damage that removes hit cells from the bone marrow. After X, gamma or 56Fe-ion irradiation, AML-resistant C57BL/6 mice have fewer cells with PU.1 deletions than CBA mice, and those cells do not persist in the bone marrow of the C57B6/6 mice. Our findings suggest that quantification of PU.1 deleted bone marrow cells 1 month postirradiation can be used as surrogate for the incidence of radiation-induced AML measured in large-scale mouse studies. If so, PU.1 loss could be used to systematically assess the potential leukemogenic effects of other ions and energies in the space radiation environment.
authors.affiliation: Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Colorado 80523, USA. ypeng@colostate.edu
authors.forename: Yuanlin
authors.initials: Y
authors.lastname: Peng
authors.forename: Natalie
authors.initials: N
authors.lastname: Brown
authors.forename: Rosemary
authors.initials: R
authors.lastname: Finnon
authors.forename: Christy L
authors.initials: CL
authors.lastname: Warner
authors.forename: Xianan
authors.initials: X
authors.lastname: Liu
authors.forename: Paula C
authors.initials: PC
authors.lastname: Genik
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Callan
authors.forename: F Andrew
authors.initials: FA
authors.lastname: Ray
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Borak
authors.forename: Christophe
authors.initials: C
authors.lastname: Badie
authors.forename: Simon D
authors.initials: SD
authors.lastname: Bouffler
authors.forename: Robert L
authors.initials: RL
authors.lastname: Ullrich
authors.forename: Joel S
authors.initials: JS
authors.lastname: Bedford
authors.forename: Michael M
authors.initials: MM
authors.lastname: Weil
mesh_terms: D000818:Animals; D002875:Chromosomes; D022202:Chromosomes, Artificial, Bacterial / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D015973:Gene Expression Regulation, Leukemic; D007501:Iron; D007938:Leukemia / Q000209:etiology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D009381:Neoplasms, Radiation-Induced / Q000209:etiology* / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D014965:X-Rays; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D007501:Iron; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1