Dynamics of cellular responses to radiation.
Understanding the consequences of exposure to low dose ionizing radiation is an important public health concern. While the risk of low dose radiation has been estimated by extrapolation from data at higher doses according to the linear non-threshold model, it has become clear that cellular responses can be very different at low compared to high radiation doses. Important phenomena in this respect include radioadaptive responses as well as low-dose hyper-radiosensitivity (HRS) and increased radioresistance (IRR). With radioadaptive responses, low dose exposure can protect against subsequent challenges, and two mechanisms have been suggested: an intracellular mechanism, inducing cellular changes as a result of the priming radiation, and induction of a protected state by inter-cellular communication. We use mathematical models to examine the effect of these mechanisms on cellular responses to low dose radiation. We find that the intracellular mechanism can account for the occurrence of radioadaptive responses. Interestingly, the same mechanism can also explain the existence of the HRS and IRR phenomena, and successfully describe experimentally observed dose-response relationships for a variety of cell types. This indicates that different, seemingly unrelated, low dose phenomena might be connected and driven by common core processes. With respect to the inter-cellular communication mechanism, we find that it can also account for the occurrence of radioadaptive responses, indicating redundancy in this respect. The model, however, also suggests that the communication mechanism can be vital for the long term survival of cell populations that are continuously exposed to relatively low levels of radiation, which cannot be achieved with the intracellular mechanism in our model. Experimental tests to address our model predictions are proposed.
Department of Ecology and Evolutionary Biology, University of California, Irvine, California, United States of America; Department of Mathematics, Rowland Hall, University of California, Irvine, California, United States of America.
Dominik
D
Wodarz
Department of Mathematics, Rowland Hall, University of California, Irvine, California, United States of America.
Ron
R
Sorace
Department of Ecology and Evolutionary Biology, University of California, Irvine, California, United States of America; Department of Mathematics, Rowland Hall, University of California, Irvine, California, United States of America.
Natalia L
NL
Komarova
D002450:Cell Communication / Q000528:radiation effects; D002477:Cells / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D008962:Models, Theoretical; D011836:Radiation Tolerance