Keywords: DNA molecules, double-strand breaks, low radiation, repair kinetics, modelling, low-dose radiation, multicellular signalling, intercellular stress response
Multicellular signalling model for DNA double-strand break repair kinetics after low-dose radiation
This paper introduces the Multicellular Signalling (MULTISIG1) model in which DNA double-strand break (DSB) repair initiation requires intercellular stress-response signalling from a threshold number of cells with DSBs, which occurs at the threshold radiation absorbed dose, T. The model applies to low radiation doses and employs an exponential distribution of times to DNA DSB repair completion with mean β. The MULTISIG1 model is found to be consistent with published data for γ-H2AX foci removal (reflecting DSB repair kinetics) after exposing cultures of confluent (non-dividing) human-derived lung fibroblast (MRC-5 line) to low-dose, 90-kV machine X-rays. T is estimated to be slightly greater than 1.2 mGy, a dose associated with, on average, about 1 electron track (form ionisations) per cell nucleus. β is estimated to be about 2.5 h and the corresponding rate of break repairs (μ) is estimated to be about 0.4 break repairs/h on different DNA molecules.