Effects of radiation on growth of two human tumour cell lines that survived a previous high dose, low dose-rate radionuclide exposure simulating intensive radionuclide therapy, were analyzed. The purpose was to investigate whether the survivors gained therapy induced changes in growth and radiation response. The U118MG, ParRes (parental resistant), and U373MG, ParSen (parental sensitive), glioma cells were used because they are known to be low dose-rate radiation resistant and sensitive, respectively. These cells were initially exposed to high dose, low dose-rate radiation for 24 h and surviving U118MG and U373MG cells formed new cultures called SurRes (surviving resistant) and SurSen (surviving sensitive), respectively. All four cell types were then exposed to graded acute radiation doses, 0-8 Gy, and analyzed for radiation induced growth disturbances. They were also analyzed regarding DNA-content and cell cycle distributions. The SurRes cells regained in most cases the same growth rate, had the same growth delays and showed generally a similar response as the original ParRes cells to the 0-8 Gy exposures. In contrast, the SurSen cells had in all cases slower growth rate and longer growth delays than the original ParSen cells after the 0-8 Gy exposures. There were no signs of radiation-induced radioresistance. The slow growing SurSen cells contained about 80% more DNA and had more cells in G1 and fewer in G2 than the ParSen cells. The conclusion is that tumour cells surviving high dose, low dose-rate, radionuclide therapy, afterwards can react differently to a new radiation exposure.

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