TY - JOUR
T1 - Radiation-induced chromosome aberrations in ataxia telangiectasia cells
T2 - High frequency of deletions and misrejoining detected by fluorescence in situ hybridization
AU - Kawata, Tetsuya
AU - Ito, Hisao
AU - George, Kerry
AU - Wu, Honglu
AU - Uno, Takashi
AU - Isobe, Kouichi
AU - Cucinotta, Francis A.
PY - 2003/5/1
Y1 - 2003/5/1
N2 - The mechanisms underlying the hyper-radiosensitivity of AT cells were investigated by analyzing chromosome aberrations in the G2 and M phases of the cell cycle using a combination of chemically induced premature chromosome condensation (PCC) and fluorescence in situ hybridization (FISH) with chromosome painting probes. Confluent cultures of normal fibroblast cells (AG1522) and fibroblast cells derived from an individual with AT (GM02052) were exposed to γ rays and allowed to repair at 37°C for 24 h. At doses that resulted in 10% survival, GM02052 cells were approximately five times more sensitive to γ rays than AG1522 cells. For a given dose, GM02052 cells contained a much higher frequency of deletions and misrejoining than AG1522 cells. For both cell types, a good correlation was found between the percentage of aberrant cells and cell survival. The average number of color junctions, which represent the frequency of chromosome misrejoining, was also found to correlate well with survival. However, in a similar surviving population of GM02052 and AG1522 cells, induced by 1 Gy and 6 Gy, respectively, AG1522 cells contained four times more color junctions and half as many deletions as GM02052 cells. These results indicate that both repair deficiency and misrepair may be involved in the hyper-radiosensitivity of AT cells.
AB - The mechanisms underlying the hyper-radiosensitivity of AT cells were investigated by analyzing chromosome aberrations in the G2 and M phases of the cell cycle using a combination of chemically induced premature chromosome condensation (PCC) and fluorescence in situ hybridization (FISH) with chromosome painting probes. Confluent cultures of normal fibroblast cells (AG1522) and fibroblast cells derived from an individual with AT (GM02052) were exposed to γ rays and allowed to repair at 37°C for 24 h. At doses that resulted in 10% survival, GM02052 cells were approximately five times more sensitive to γ rays than AG1522 cells. For a given dose, GM02052 cells contained a much higher frequency of deletions and misrejoining than AG1522 cells. For both cell types, a good correlation was found between the percentage of aberrant cells and cell survival. The average number of color junctions, which represent the frequency of chromosome misrejoining, was also found to correlate well with survival. However, in a similar surviving population of GM02052 and AG1522 cells, induced by 1 Gy and 6 Gy, respectively, AG1522 cells contained four times more color junctions and half as many deletions as GM02052 cells. These results indicate that both repair deficiency and misrepair may be involved in the hyper-radiosensitivity of AT cells.
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U2 - 10.1667/0033-7587(2003)159[0597:RCAIAT]2.0.CO;2
DO - 10.1667/0033-7587(2003)159[0597:RCAIAT]2.0.CO;2
M3 - Article
C2 - 12710870
AN - SCOPUS:0037964269
VL - 159
SP - 597
EP - 603
JO - Radiation Research
JF - Radiation Research
SN - 0033-7587
IS - 5
ER -