SUBSTRUCTURE IN THE CELL-SURVIVAL RESPONSE AT LOW RADIATION-DOSE - EFFECT OF DIFFERENT SUBPOPULATIONS

In order to obtain more accurate measurements of cell survival after l ow doses of radiation, we have used the cell sorter assay, in which a cell sorter is used to accurately count out the number of cells plated for colony formation. This method, combined with data averaging, perm its measurements of survival with superior precision, which have revea led that there is substructure in the radiation response of asynchrono usly dividing Chinese hamster cells. The substructure, observed at dos es of a few Gy, has features of a 2-component response, consistent wit h the presence of subpopulations of cells of different cell-cycle-rela ted radiosensitivity. The absence of any substructure in the radiation response of homogeneous (tightly synchronized) cell populations lends strong support to this subpopulation explanation of the substructure. This assay has also been used on a variety of human tumour cell lines , most of which exhibited substructure similar to that of Chinese hams ter cells. This paper outlines the application of the cell sorter assa y to three different problems: (i) radiosensitizer mechanisms-etanidaz ole and RB 6145 are shown to enhance primarily the beta term and alpha term, respectively, of tumour cell kill, indicating that sensitizer e fficacy may be tumour-specific and predictable from tumour response pa rameters; (ii) accurate measurement of Relative Biological Effectivene ss (RBE) in a modulated clinical proton beam shows that the RBE is bot h dose- and depth- dependent; and (iii) measurements at lower doses cl early demonstrate a second order of substructure, termed the hypersens itive response, at doses < 1 Gy.