Analysis of radiation-induced chromosomal aberrations on cell-by-cell basis after 4He-ion microbeam irradiation: experimental data and simulations

Various aspects of chromosomal aberration induction by means of ionizing radiation still need to be clarified, including correlation with the radiation track - structure. Within the EMRP Joint Research Project “BioQuaRT” (Biologically weighted Quantities in Radio Therapy), an experimental and theoretical analysis was carried out on chromosomal aberrations in Chinese hamster ovary cells (CHO-K1) exposed to α particles with final energies at the target of 5.5 MeV and 17.8 MeV, which were generated by a microbeam available at PTB in Braunschweig (Germany). In line with the differences in LET (which was about 85 keV/m for 5.5 MeV α particles and about 36 keV/m for 17.8 MeV α particles), the 5.5 MeV α particles were more effective than the 17.8 - MeV α particles, both in terms of the percentage of aberrant cells (which was 57 % vs. 33 %) and in terms of the aberration frequency. The yield of total aberrations increased by a factor of 2, although the D+R category (dicentrics plus centric rings) showed a less pronounced increase than the acentrics category. The experimental data were compared with Monte Carlo simulations based on a biophysical model called BIANCA (BIophysical ANalysis of Cell death and chromosomal Aberrations); basing on such comparisons, the experimental results were interpreted in terms of DNA critical damage (“Cluster Lesions”, CLs). More specifically, the higher aberration yields observed for the 5.5 MeV α particles were explained by taking into account the fact that, although the nucleus was traversed by fewer particles (nominally, 11 vs. 25), each particle was much more effective (by a factor of 4) at inducing CLs. This led to an increased yield of CLs/cell (by a factor of 2), consistent with the increased yield of total aberrations observed in the experiments.