HIGH SPLIT-DOSE RECOVERY IN HYPERSENSITIVE HUMAN FIBROBLASTS - A CASEOF INDUCED RADIORESISTANCE

We studied the extent of split-dose recovery in seven non-transformed human fibroblast cell lines of different intrinsic radiosensitivity (H F19, 1BR3, 149BR, 84BR, GM739, 180BR, and AT2EM). Experiments were per formed on both growing and plateau-phase cells. The seven cell lines d isplayed a wide range of intrinsic radiosensitivity. The (D) over bar of plateau phase cells ranged from 0.56 (AT2EM) to 3.02 Gy (HF19). The recovery ratios (RR) of the three non-ataxic hypersensitive cell line s (84BR, GM739, and 180BR) were significantly higher than those predic ted from the single-dose survival curves of both growing and plateau-p hase cells. In addition, in these three hypersensitive cell lines the challenge dose survival curve generated after different priming doses showed a reduction in the intrinsic radiosensitivity; the high RRs obs erved were due both to beta and a reduction in alpha. This suggests th at a protective mechanism may be triggered by the first irradiation le ading to induced radioresistance. For growing cells, the relationship between 1n RR and 2d(2) was well fitted by linear regression. With pla teau phase cells, RR appeared to be dose dependent in a more complex f ashion. Thus, no single value of beta(RR) was representative of the sp lit-dose recovery. With the ataxic cell line AT2EM, the split-dose stu dies detected a limited capacity to recover in spite of the beta value of the single dose survival curve being nil.