Low-dose radiation hyper-radiosensitivity in multicellular tumour spheroids

Abstract

Objective: We propose and study a new model aimed at describing the low-dose hyper-radiosensitivity phenomenon appearing in the survival curves of different cell lines.

Methods: The model uses the induced repair assumption, considering that the critical dose at which this mechanism begins to act varies from cell to cell in a given population. The model proposed is compared with the linear-quadratic model and the modified linear-quadratic model, which is commonly used in literature and in which the induced repair is taken into account in a heuristic way. The survival curve for the MCF-7 line of human breast cancer is measured at low absorbed doses and the uncertainties in these doses are estimated using thermoluminiscent dosemeters.

Results: It is shown that these multicellular spheroids present low-dose hyper-radiosensitivity. The new model permits an accurate description of the data of two human cell lines (previously published) and of the multicellular spheroids of the MCF-7 line here measured.

Conclusion: The model shows enough flexibility to account for data with very different characteristics and considers in a faithful way the hypothesis of the repair induction.

Figure 1

Situation of the samples for the irradiation in a Theratron 780 unit (Best Theratronics, Ottawa, Canada). (a) The culture boxes for spheroids are situated at a depth of 20 cm inside a phantom formed of RW3 slabs of 30×30×1 cm. (b) To reproduce the dosimetric conditions of the irradiation, and taking into account the symmetry of the beam used, we can consider the two possible positions (labelled 1 and 2 in the figure) of the samples in the phantom.

Figure 2

Scheme of regrowth of irradiated multicellular tumour spheroids (MCTSs). Dotted line represents the volume of sterilised cells, dashed line that of the survival ones and solid line the total MCTS volume. These results correspond to V₀=30×10⁶ μm³, V₀^surv=5×10⁶ μm³, A=4.5 and a=0.08 days.

Figure 3

Comparison between the models studied in this work. (a) The survival fraction given by Equation (10) is plotted with a dashed line, the full Monte Carlo calculation with squares and the restricted Monte Carlo calculation with a solid line. (b) The proposed variable induced repair model (dashed line) is compared with the induced repair (solid line) and the linear-quadratic (dotted line) model. In both panels, the dotted vertical line indicates the critical dose d_c for the repair stimulation. See the text for the parameters used for the various models.

Figure 4

Fit of the survival model proposed in this work to experimental data published for the cell line T98G of human glioblastoma [35]. The fits obtained using the linear-quadratic (LQ) and induced repair (IR) models are plotted as well. A detail of the region in which the induced repair occurs is shown in the inset. VIR, variable induced repair.

Figure 5

Fit of the survival model proposed in this work to experimental data published for the cell line L132 of human lung epithelial cells [31]. The fits obtained using the linear-quadratic (LQ) and induced repair (IR) models are plotted as well. A detail of the region in which the induced repair occurs is shown in the inset. VIR, variable induced repair.

Figure 6

Fit of the survival model proposed in this work [Equation (13)] to the survival data found for the MCF7 clone BB cell line of breast cancer. The fits obtained using the linear-quadratic (LQ) and induced repair (IR) models are plotted as well. Uncertainties correspond to a coverage factor k=1. VIR, variable repair model.

Figure 7

Lognormal distribution of d_c [Equation (14)] for each of the cell lines considered in this work.