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

Abstract

Abstract. 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 singledose 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 RR s 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 2 d 2 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.