Relative contribution of bystander and targeted cell killing to the low-dose region of the radiation dose-response curve

Human keratinocytes show a bystander effect when exposed to low doses of lo w-LET radiation, In this paper, data are presented showing a method of corr ecting the overall survival curve to enable analysis of the relative contri butions of the bystander effect and the effect attributable to direct inter action of the radiation with the target cell. The technique used is to obta in a standard clonogenic survival curve using the assay of Puck and Marcus and, with a different set of flasks containing cloning densities of unirrad iated cells, to assay the cell killing caused by medium harvested from 2 x 10(5) cells irradiated with the same doses. The data show that for this hum an epithelial cell line, doses of 0.01-0.5 Gy show clonogenic death by the bystander effect only, if maximum potential bystander killing is assumed. T he magnitude of the effect is relatively constant, and it appears to satura te at doses in the range of 0.03-0.05 Gy, After doses greater than 0.5 Gy, the curves for clonogenic death are the result of a dose-dependent non-byst ander effect and a dose-independent bystander effect. If these particular d ose-response effects occur in epithelial cells in vivo, they may have impor tant consequences for therapy and studies of low-dose risk. (C) 2000 by Rad iation Research Society.