Effects of low dose irradiation on TK6 and U937 cells: induction of p53 and its role in cell-cycle delay and the adaptive response

Purpose: To investigate the effect of small doses of radiation on the cell- cycle and related processes, and to determine the capacity of small doses o f radiation to induce an adaptive response. Materials and methods: TK6, a lymphoblast cell line with wild-type p53, and U937, a monocytic leukaemia cell line with mutant, inactive, p53 were expo sed to gamma ray doses ranging from 0.1 Gy to 3 Gy. Cell-cycle distribution s and cyclin B1 were assessed by flow cytometry and p53 and p21 protein lev els were measured by western blotting. Apoptosis was determined by fluoresc ence microscopy after staining with Hoechst 33342, and by measurement of th e pre-G1 cell population by flow cytometry. Micronuclei were determined in cytokinesis-blocked cells by fluorescence microscopy. Results: In TK6 cells, radiation exposure induced elevated p53 and p21 leve ls and delayed expression of cyclin B1. No changes in these parameters were found in U937 cells. Although both cell lines arrested in G2/M after large r doses of radiation, G2/M-arrest occurred after 0.1 Gy and 0.3 Gy in TK6 c ells only. An apoptotic adaptive response was induced in both cell lines by a 0.1 Gy priming dose but an adaptive response with respect to micronuclei was observed only in U937 cells. Conclusions: The radiation adaptive response can occur in the absence of wi ld-type p53. A small dose of radiation may nor protect cells against both a poptosis and cytogenetic damage caused by a subsequent larger dose of radia tion.