Cytotoxic and mutagenic effects of chronic low-dose-rate irradiation on TERT-immortalized human cells.
To analyze the genetic effects of low-dose-rate radiation on human cells, we used human telomere reverse transcriptase (TERT)-immortalized fibroblast cells obtained from normal individuals. We studied the effect of low-dose-rate (0.3 mGy/ min) and high-dose-rate (2 Gy/min) radiation on cells in a confluent state. Survival and micronucleus induction frequency showed higher resistance after irradiation at low dose rate than at high dose rate. The survival after 5 Gy of high-dose-rate radiation was 0.01 compared to 0.3 after low-dose-rate irradiation at the same dose. In accordance with this, the level of HPRT mutation induction by low-dose-rate radiation decreased to approximately one-eighth that for high-dose-rate radiation. We then characterized the mutants by multiplex PCR analysis, which showed that the fraction of deletion mutations was lower in the mutant cells induced at low dose rate than at high dose rate. Furthermore, the size of the deletions in mutant cells induced by low-dose-rate radiation appeared to be smaller than those in mutant cells irradiated at high dose rate. Only a few exons were deleted in the former mutants while all exons were deleted in most of the latter mutants. The present study indicates that the genetic effects of low-dose-rate radiation on nonproliferating normal human cells are quantitatively and qualitatively less severe than the effect of high-dose-rate radiation.
Nakamura
Hideaki
H
Central Laboratory and Radiation Biology, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan. hnakamu@aichi-cc.jp
Fukami
Hiroko
H
Hayashi
Yuko
Y
Tachibana
Akira
A
Nakatsugawa
Shigekazu
S
Hamaguchi
Michinari
M
Ishizaki
Kanji
K
D002470:Cell Survival / Q000528:radiation effects; D002869:Chromosome Aberrations; D004268:DNA-Binding Proteins; D004307:Dose-Response Relationship, Radiation; D005091:Exons; D005347:Fibroblasts / Q000378:metabolism; D017353:Gene Deletion; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008297:Male; D015162:Micronucleus Tests; D009153:Mutagens; D009154:Mutation; D016133:Polymerase Chain Reaction; D012044:Regression Analysis; D019098:Telomerase / Q000378:metabolism*
D004268:DNA-Binding Proteins; D009153:Mutagens; D007041:Hypoxanthine Phosphoribosyltransferase; C509186:TERT protein, human; D019098:Telomerase