Abstract
Curves of growth delay (GD) or 'cure' after graded doses of radiation have been analysed for 16 lines of human and animal tumours grown as multicellular spheroids in vitro. Dose-survival curves were derived for those cellular units from which spheroids regrow after unsuccessful irradiation (spheroid-regenerating cellular units, SRU). For 10 sets of data from 6 spheroid lines, the Do's and extrapolation numbers of the SRU derived by GD could be compared with the response of the clonogenic cells of the spheroids. For Do, a good correlation (r = 0.910) was found between the two; this was true also for Do derived from curves of spheroid 'cure' (7 sets of data from 6 spheroid lines) and clonogenic cells (r = 0.986). Using GD, the correlation of extrapolation numbers was less good (r = 0.682), the values for SRU commonly being higher than those for clonogenic cells. This may reflect features of the growth curves of spheroids after the lower range of doses of radiation. For human and animal tumour spheroids of 250 microns or less, derived Do ranged from 0.5 to 2.5 Gy. For spheroids of 350 microns or more, derived Do for animal tumour lines ranged from 3.4 to 4.2 Gy, for human lines from 1.5 to 2.1 Gy.
Highlights
The following simplifying assumptions were made, following Wheldon et al (1985): (i) that the number of spheroidregenerating cellular units (SRU) within a spheroid at the time of irradiation is proportional to its volume at that time. (ii) that the rate of growth of a spheroid or of its regrowth after irradiation is the same, i.e. there are no dose-dependent effects other than a G2 block that causes an initial delay in the regrowth of the SRU population. (iii) that part at least of the observed curve of regrowth in volume versus time after irradiation can be approximated by a single exponential function and that this function describes the regrowth of the constituent SRU from the initial number that survived irradiation
Other publications contain growth delay (GD) curves that may be analysed to determine the range of values for sensitivity of SRU to be expected from this method
For all tumour lines analysed here from both studies, repair of potentially lethal damage by clonogenic cells was said not to occur, i.e. the time of disaggregation did not change the shape of survival curves for clonogenic cells
Summary
The following simplifying assumptions were made, following Wheldon et al (1985): (i) that the number of spheroidregenerating cellular units (SRU) within a spheroid at the time of irradiation is proportional to its volume at that time. (ii) that the rate of growth of a spheroid or of its regrowth after irradiation is the same, i.e. there are no dose-dependent effects other than a G2 block that causes an initial delay in the regrowth of the SRU population. (iii) that part at least of the observed curve of regrowth in volume versus time after irradiation can be approximated by a single exponential function and that this function describes the regrowth of the constituent SRU from the initial number that survived irradiation. (ii) that the rate of growth of a spheroid or of its regrowth after irradiation is the same, i.e. there are no dose-dependent effects other than a G2 block that causes an initial delay in the regrowth of the SRU population. (iii) that part at least of the observed curve of regrowth in volume versus time after irradiation can be approximated by a single exponential function and that this function describes the regrowth of the constituent SRU from the initial number that survived irradiation. The back-extrapolates of these fitted curves for the different doses gave the surviving fractions (SF) of SRU. The program calculated a best-fit curve and yielded values for the reciprocal of the final exponential slope (Do) of the curve and its extrapolation number (E)
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