hTERT-immortalized cells useful for analyzing effects of low-dose-rate radiation on human cells

To establish immortal human cells, we introduced the cDNA of the human telomere reverse transcriptase (hTERT) gene into skin fibroblast cells obtained from normal and ataxia telangiectasia (AT) individuals of Japanese origin. hTERT-immortalized cells retained their original characteristics and radiosensitivity except for immortalization, suggesting that these cells might be useful for analyzing the effects of radiation on human cells.hTERT-immortalized cells from a normal individual showed a greater resistance after low-dose-rate irradiation than after high-dose-rate irradiation. In contrast, cells from AT patients irradiated at a low-dose rate showed virtually the same survival as those irradiated at a high-dose rate. In hTERT-immortalized normal cells, the genetic effects of low-dose-rate radiation were quantitatively and qualitatively less severe than those of high-dose-rate radiation. In hTERT-immortalized AT cells, some fraction of DNA damage such as DNA double-strand breaks might not be repaired, and AT cells were severely affected by low-dose-rate radiation. The activation of ataxia telangiectasia mutated (ATM) protein was confirmed during low-dose-rate radiation, and may play an important role in repair of DNA damage induced by low-dose-rate radiation. This paper reviews briefly the current research at our laboratory. The hTERT-immortalized cells may be useful in determining the effects of low-dose and low-dose-rate radiation on human cells.