NEW DERIVATION, FROM SPLIT-DOSE DATA, OF THE COMPLETE SURVIVAL CURVE FOR CLONOGENIC NORMAL-CELLS INVIVO

A method is described for completing the shoulder region of survival curves for clonogenic cells that are grouped into multicellular structures, for which the multiplicity produces a threshold region at low single doses, which masks the shoulder of the single-cell survival curve. The method uses split-dose irradiation, with a time interval considered sufficient for restitution of the original dose-response relationship. First, large equal split doses are used to provide a surviving fraction for the second dose (assumed equal to that for the first), and survival values for higher single doses are calculated with reference to the latter. Second, survival levels for lower single doses are deduced from the additional effect of small doses over their large-dose counterparts. New data are presented and analyzed for mouse jejunal crypts, and published data for gastric crypts and spermatogonia (which regenerate tubules) are similarly analyzed. A close similarity is seen between the response of gastric cryptogenic cells and spermatogenic cells, with jejunal cryptogenic cells being slightly more sensitive.