Dissociation between radioresistant DNA replication and chromosomal radiosensitivity in ataxia telangiectasia cells.
Ataxia telangiectasia (AT) skin fibroblasts in G1 phase and peripheral blood lymphocytes in G0 and G1 phase were studied for their DNA replication response to X-rays. The irradiation of normal cells in G1 but not in G0 phase caused a delay of onset of DNA replication, which was less pronounced in AT cells. However, such radioresistant DNA replication itself cannot be the sole mechanism of the increased sensitivity of AT cells to chromosome aberration formation by X-rays for the following two reasons: (1) due to the intrinsically slow cell cycle progression of AT fibroblasts, the time of traverse to DNA replication of AT cells was comparable with that of normal cells after exposure to 1 Gy while AT cells gave rise to a greatly increased number of chromatid aberrations; (2) in peripheral blood lymphocytes irradiated in G0 phase, the traversal to the DNA replication phase was the same for normal and AT cells in spite of the well documented chromosomal radiosensitivity of G0-irradiated AT cells. The AT factor may be better explained as a key element directly involved in DNA damage processing, which in turn provides messages to suppress replication if recombination and replication are mutually exclusive.
Sasaki
M S
MS
Radiation Biology Center, Kyoto University, Japan.
Taylor
A M
AM
D000293:Adolescent; D000328:Adult; D001260:Ataxia Telangiectasia / Q000235:genetics*; D002453:Cell Cycle / Q000528:radiation effects; D002478:Cells, Cultured; D002648:Child; D002877:Chromosomes, Human / Q000528:radiation effects*; D004261:DNA Replication / Q000528:radiation effects*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000528:radiation effects; D006801:Humans; D008297:Male