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 γ Rays. Part I. Experimental observations

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 γ-, 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 γ 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, γ 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.