H. Beamish et Mf. Lavin, RADIOSENSITIVITY IN ATAXIA-TELANGIECTASIA - ANOMALIES IN RADIATION-INDUCED CELL-CYCLE DELAY, International journal of radiation biology, 65(2), 1994, pp. 175-184
Citations number
46
Categorie Soggetti
Radiology,Nuclear Medicine & Medical Imaging","Nuclear Sciences & Tecnology
A number of anomalies have been described in the progression of ataxia
-telangiectasia (AT) cells through the cell cycle post-irradiation. So
me uncertainty still exists as to whether AT cells show increased or r
educed division delay after exposure to ionizing radiation. We have at
tempted to resolve the apparent inconsistencies that exist by investig
ating the effects of radiation on AT cells at various stages of the ce
ll cycle. Specific labelling of S phase cells with 5-bromodeoxyuridine
(BrdU) followed by irradiation caused a prolonged accumulation of the
se cells in G(2)/M phase with only 2-7% of AT cells progressing throug
h to G(1) 24h post-irradiation. In contrast, 23-28% of control cells i
rradiated in S phase reached G(1) by 24h after irradiation. As observe
d previously with AT fibroblasts, AT lymphoblastoid cells irradiated i
n G(1) phase did not experience a delay in entering S phase. After pro
gressing through S phase these cells also were delayed in G(2)/M, but
not to the same extent as irradiated S phase cells. On the other hand,
when AT cells were irradiated in G(2) phase they showed less delay in
itially in entry to mitosis and the subsequent G(1) phase than did irr
adiated control cells. The overall results demonstrate that AT cells f
ail to show an initial delay in transitions between the G(1)/S and G(2
)/M phases of the cell cycle and in progression through these phases p
ost-irradiation, but in the long-term, after passage through S phase,
they experience a prolonged delay in G(2)/M. Since several AT compleme
ntation groups are represented in this study, the cell cycle anomalies
appear to be universal in AT. These results implicate deficiencies in
control of cell cycle progression in the increased radiosensitivity a
nd cancer predisposition in AT.