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Lymphocyte radiosensitivity: An extension to the linear-quadratic model?
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CERVOXY. International audience. Background and purpose: The linear-quadratic (LQ) model has been pivotal for evaluating the effects of radiationon cells, but it is primarily characterized by linear responses, which has exhibited limitations when applied tolymphocyte data. The present research aims to address these limitations and to explore an alternative modelextended from the conventional LQ model.Materials and methods: literature providing lymphocyte counts from assays investigating apoptosis and survivalafter in vitro irradiation was selected. To address the nonlinearity in lymphocyte responses to radiation, wedeveloped a saturation model characterized by a negative exponential relationship between radiation dose andcellular response. We compared the performance of this saturation model against that of conventional models,including the LQ model and its variants (linear model LM and linear-quadratic-cubic model LQC), as well as therepair-misrepair (RMR) model. The models were evaluated based on prediction-residual plots, residual standarderrors, and the Akaike information criterion (AIC). We applied the saturation model to two additional datasets:(1) a dataset from the existing literature that assessed stimulated and unstimulated human lymphocytes exposedto gamma irradiation in vitro and (2) a novel dataset involving T lymphocytes from rodent spleens after exposureto various radiation types (X-rays and protons).Results: The literature (n=15 out of 2342) showed that lymphocyte apoptosis varies with dose, time andexperimental conditions. The saturation model had a lower AIC of 718 compared to the LM, LQ, LQC and RMRmodels (AIC of 728, 720, 720 and 734, respectively). The saturation model had a lower residual error and moreconsistent error distribution. Integrating time as a covariate, the saturation model also had a better AIC fordemonstrating time-dependent variations in lymphocyte responses after irradiation. For datasets involvingunstimulated lymphocytes before irradiation, the saturation model provided a more accurate fit than did the LM,LQ, and RMR models. In these cases, the fit of the saturation model was comparable to that of the LQC model butoffered an advantage when extrapolating to higher doses, where the LQC model might underestimate survival.For stimulated lymphocytes, which are radioresistant, all the models approximated the LM. Both the LQ andsaturation models indicated greater radiosensitivity to protons in vitro.Conclusion: The new “saturation model” performed better than the LQ model in quantifying lymphocyteapoptosis and survival, estimating time dependency and assessing the role of radiation modalities or lymphocytestimulation. Further experiments are warranted to experimentally explore the validity of the saturation model asa promising alternative in the clinical setting.
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