SUBSTRUCTURE IN THE RADIATION SURVIVAL RESPONSE AT LOW-DOSE IN CELLS OF HUMAN TUMOR-CELL LINES

In earlier studies using asynchronously growing Chinese hamster cells, we observed substructure in the survival response at low doses. The s ubstructure appeared to result from subpopulations of cells having dif ferent, cell cycle phase-dependent radiosensitivity. We have now appli ed the same flow cytometry and cell sorting technique to accurately me asure the responses of cells of eight different asynchronously growing human tumor cell lines, representing a wide range in radiosensitivity . When the data were fitted with a linear-quadratic (LQ) function, mos t of these lines showed substructure similar to that observed in Chine se hamster cells, with the result that values of alpha and beta were d ependent on the dose range used for fitting. Values of alpha describin g the low-dose response were typically smaller (by as much as 2.2 time s) than the alpha describing the high-dose response, while values of b eta were larger at low doses. Values of alpha/beta from our measuremen ts are in reasonable agreement with other values published recently if we fit the data for the high-dose range (excluding, for example, 0-4 Gy), which corresponds to a conventional survival response measurement . However, the values of alpha/beta describing the low-dose range were , on average, 2.8-fold smaller. The results show that the usual labora tory measurement of cell survival over 2 or 3 logs of cell killing, if fitted with a single LQ function, will yield alpha and beta values wh ich may give a rather poor description of cell inactivation at low dos e in asynchronous cells, no matter how carefully those measurements ar e done, unless the low-dose range is fitted separately. The contributi on of killing represented by the beta coefficient at low doses was fou nd to be surprisingly large, accounting for 40-70% of cell inactivatio n at 2 Gy in these cell lines. A two-population LQ model provides exce llent fits to the data for most of the cell lines though, as one might expect with a five-parameter model, the best-fitting value of the var ious parameters is far from unique, and the values are probably not re liable indicators of the size and radiosensitivity of the different ce ll subpopulations. At very low dose, below 0.5-1 Gy, another order of substructure is observed: the hypersensitive response; this is describ ed in the accompanying paper (Wouters et al., Radiat. Res. 146, 399-41 3, 1996). (C) 1996 by Radiation Research Society