Radiation model and simulation of spheroid response to radiation using the SABM.

(A) A LQ radiation model was parameterised by measuring clonogenic cell survival of HCT116 monolayer (105 cells/mL) in response to a range of radiation doses under anoxic (unfilled rectangles in A, 3 separate experiments) or oxic (unfilled triangles in A, 2 separate experiments) conditions. Values are means ± SEM. Lines represent LQ model fits (Eqn S12) to all monolayer data simultaneously (fitted parameters in Table 1) by minimization of the sum of squared errors between simulated and observed ln(SF). These parameters were used in the SABM to simulate clonogenic cell survival of cells in 4-day spheroids exposed to radiation under 20% O2 (solid line in A) and compared to measured clonogenic cell killing in HCT116 spheroids (filled circles in A). Values are means ± SD (n = 16 spheroids). To compare the measured spheroid growth delay induced by radiation to that predicted by the SABM, HCT116 spheroids were exposed to 4 Gy radiation under 5% (Panel B) or 20% O2 (Panel C) and spheroid growth was monitored as a function of time. Values are means ± SD (n = 16 spheroids) and lines are simulations by the SABM based on clonogenic cell killing alone (…), or with addition of parameters for cell growth inhibition and survival probability at each mitosis following radiation (—) as described in Table 1.