High split-dose recovery in hypersensitive human fibroblasts: a case of induced radioresistance?

We studied the extent of split-dose recovery in seven non-transformed human fibroblast cell lines of different intrinsic radiosensitivity (HF19, 1BR3, 149BR, 84BR, GM739, 180BR and AT2EM). Experiments were performed on both growing and plateau-phase cells. The seven cell lines displayed a wide range of intrinsic radiosensitivity. The D 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 lines (84BR, GM739, and 180BR) were significantly higher than those predicted from the single-dose survival curves of both growing and plateau-phase 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 observed were due both to beta and a reduction in alpha. This suggests that a protective mechanism may be triggered by the first irradiation leading to induced radioresistance. For growing cells, the relationship between ln RR and 2D2 was well fitted by linear regression. With plateau phase cells, RR appeared to be dose dependent in a more complex fashion. Thus, no single value of beta RR was representative of the split-dose recovery. With the ataxic cell line AT2EM, the split-dose studies detected a limited capacity to recover in spite of the beta value of the single dose survival curve being nil.