INCREASING RADIOSENSITIVITY IN THE COURSE OF FRACTIONATED X-IRRADIATION - THE EFFECT OF CONTACT WITH DEAD AND DYING CELLS

We have measured survival after successive 2-Gy doses of X rays in HeL a cells and 1-Gy doses in cells of the nonimmortalized human fibroblas t cell line AG15-22 under conditions where any effect of cell prolifer ation during multifraction X irradiation has been factored out. When H eLa cells in parallel series of (pseudo)hybrid spheroids (i.e. in aggl omerates consisting of a mixture of supralethally irradiated HeLa feed er and viable HeLa cells) were exposed to n daily radiation doses and then trypsinized and exposed to the last dose, the surviving fraction at 2 Gy (SF2) declined exponentially from 0.55 +/- 0.01 to 0.31 +/- 0. 01 after the fifth fraction. In monolayer HeLa cell cultures, the decl ine in SF2 was smaller but significant and was not influenced by the p resence of feeder cells. Pure spheroids, composed entirely of viable H eLa cells, showed the same decline in SF2 as did monolayer cells. The cumulative;effect curve (i.e. the product of SF2 values) was linear-qu adratic with the quadratic term increasing in the order monolayer, pur e spheroids, pseudohybrid spheroids. SF2(n) and D-0Eff (deduced from t he initial SF2) severely underestimated cumulative radiosensitivity. T his cumulative effect is clearly associated with the proximity of leth ally irradiated cells and might be explained by differential populatio n shifts in the course of the multifraction regimen. Similarly, AG15-2 2 cells irradiated with daily 1-Gy doses of X rays showed a larger inc rease in radiosensitivity when in hybrid spheroids than when in pure s pheroids. However, for the AG15-22 cells, SF1 was twofold lower for th e former than for the latter condition and remained constant for both conditions rather than decreasing with increasing fraction number. Thi s large radiosensitizing effect remains unexplained. (C) 1998 by Radia tion Research Society.