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 II. Theoretical considerations based on microdosimetry and the initial induction of chromosome aberrations

Chromosome aberrations in mitotic bone marrow cells of CBA/Ca and C57BL/6 mice were measured 1 day after exposure to 1 Gy of 1 GeV/nucleon ⁵⁶Fe ions or 3 Gy of γ rays. The proportion that have lost a region of chromosome 2 containing the PU.1 gene could be explained by a model based on these measurements. The distribution of aberrations among cells was close to the expected Poisson for the γ-irradiated cells, but for the HZE ⁵⁶Fe ions the distribution was highly dispersed. The observations were consistent with the results of an analysis similar to that of Edwards and co-workers in 1980 after ex vivo irradiation of human blood with α particles. The analysis used to fit the current data was based on a compound Poisson process, also used previously by others, but in addition included the random nature of parameters involved such as cell nuclear diameter, particle traversal lengths through cell nuclei, production of aberrations, and cell cycle arrest per traversal. From the measured numbers of acentric fragments produced, the relative size of chromosome 2 and the region associated with PU.1 deletions, an independent prediction of PU.1 loss agreed well with measurements described in the accompanying paper.