Modeling cell response to low doses of photon irradiation--Part 1: on the origin of fluctuations

Intra- and inter-individual variability is a well-known aspect of biological responses of cells observed at low doses of radiation, whichever the phenomenon considered (adaptive response, bystander effects, genomic instability, etc.). There is growing evidence that low-dose phenomena are related to cell mechanisms other than DNA damage and misrepair, meaning that other cellular structures may play a crucial role. Therefore, in this study, a series of calculations at low doses was carried out to study the distribution of specific energies from different irradiation doses (3, 10 and 30 cGy) in targets of different sizes (0.1, 1 and 10 μm) corresponding to the dimensions of different cell structures. The results obtained show a strong dependence of the probability distributions of specific energies on the target size: targets with dimensions comparable to those of the cell show a Gaussian-like distribution, whereas very small targets are very likely to not be hit. A statistical analysis showed that the level of fluctuations in the fraction of aberrant cells is only related to the fraction of aberrant cells and the number of irradiated cells, regardless of, for instance, the heterogeneity in cell response.