Dose dependence of the growth rate of multicellular tumour spheroids after irradiation

Abstract

The present study investigated differences in the growth rate of multicellular tumour spheroids of the MCF-7 line of human breast cancer before and after their irradiation. Growth of the spheroids was analysed according to a model based on a Gompertz function. In this model, normalization to a common initial volume is achieved in a way that enables meaningful comparisons to be made between the results obtained for each spheroid. For irradiated spheroids the model includes an additional term to take account of sterilized cells. We found that the growth rate observed before irradiation is not fully recovered by irradiated spheroids and that growth recovery reduces with higher irradiation doses. Surviving fractions obtained at doses below 3 Gy are comparable with those found in clonogenic assays on spheroids of the same cellular line. At larger doses, discrepancies between the different studies are considerable.

Low-dose radiation hyper-radiosensitivity in multicellular tumour spheroids

“…The British Journal of Radiology, October 2012and nutrients was similar for all the cells forming the aggregate [28,30]. In these conditions one can expect that all cells will present a more homogeneous response to irradiation, and also that the proportionality between the volume of the spheroid and the number of cells it includes applies.…”

“…To characterise the growth of each spheroid, Equation (1) is fitted to the volumes measured for each aggregate, obtaining the corresponding values V(t 0 50);V 0 , A9 and a. To compare the growth curves of different spheroids, they must be normalised as described by Guirado et al [28]. This normalisation does not affect the parameter a, but A9 must be transformed for each spheroid, according to:…”

“…To analyse the irradiated MCTSs, we used the model developed by Guirado et al [28]. The main assumption in this model is that the volume of the spheroid can be split as:…”

“…The ability of this model to describe adequately the growth of MCTS (irradiated or not) and determine the surviving fraction after irradiation has been established by Guirado et al [28]. The main advantage of the regrowth assay with respect to the clonogenic one (both using MCTS) is the minimal perturbation of the system, as the most delicate operation during the experiment is the change of the culture medium every 3 days.…”

“…Our group has developed a method that permits us to determine the MCTS radiosensitivity with enough accuracy and with a minimum perturbation of the experimental samples [28]. As indicated above, these conditions are optimal to show LDHRS, if the phenomenon exists for the cell population under study.…”