The dose-response relationship for epithelial cells of skin.

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Atechnic has been developed for cloning epithelial cells of mouse skin. This method makes it possible to establish dose-survival curves for these cells and, in addition, to study the kinetics of recovery at the cellular level in skin. All experiments were performed in situ on the mouse back to simulate the situation obtaining in radiotherapy. If single surviving epithelial cells will regrow, and the results of these experiments suggest that they will, then it is possible to take a known initial population of cells, expose them to a known dose of radiation, D, and count the survivors. The numbers of survivors may then be expressed as a fraction of the initial population, as with in vitro cell-plating experiments. The initial population of epithelial cells is isolated from surrounding skin by an annulus of lethally irradiated cells, and this isolated area then exposed to the experimental dose D. If D is large enough, all the epithelial cells will be sterilized and complete ulceration will follow. If one or more cells survive, then a nodule of skin will regrow, becoming visible in about fourteen days. This cloning technic has the disadvantage that, because all the cells are left in situ throughout, the plating area is the same as the initial area, and, since this area is small, distinguishing one regrowing clone from another is usually impossible because of confluence before they are visible. The dose D must, therefore, be great enough to produce 0 survivors (i.e., complete ulceration) in a proportion of cases, so that the nodules observed in the remaining proportion are formed from a Poisson distribution of 1, 2, 3 etc. cells. By scoring the proportion with 0 surviving cells, the numbers of survivors may be calculated from the Poisson formula and expressed as a fraction of the initial population. By making these observations at 2 to 4 levels of survival for a constant initial population and then expanding the initial population over a thousandfold range, a dose survival curve covering several decades may be established. By using 29 kVp x rays in doses from 900 to 2,300 rads, a survival curve with a value of D0 = 135 rads was obtained. The technic is not suitable for establishing the extrapolation number from single dose experiments because the number of cells per unit area, and therefore the origin of the survival curve, cannot be accurately determined. Furthermore, the initial part of the curve (i.e. at doses less than 900 rads) cannot be defined by experimental points because of the difficulty in isolating small numbers of cells as the initial population.