Ae. Meijer et al., High-LET radiation induces apoptosis in lymphoblastoid cell lines derived from ataxia-telangiectasia patients, INT J RAD B, 77(3), 2001, pp. 309-317
Purpose: To investigate and compare the propensity of Epstein-Barr virus (E
BV)-transformed lymphoblastoid cell lines (LCL), derived from ataxia-telang
iectasia (A-T) patients and from unaffected healthy individuals (controls),
to undergo apoptosis after exposure to high-linear energy transfer (LET) r
adiation.
Materials and methods: Four A-T (ARO, BMA, CSA and RJO) and two control (JA
C and KKB3) LCL were exposed to doses of up to 4 Gy of accelerated nitrogen
ions (32-45 MeV/u, 8-12 Gy/min). For comparative purposes X-ray irradiatio
n (1.36 Gy/min) was also performed. The induction of apoptosis was studied
0-48 h after irradiation with the use of two methods: (1) monitoring of hig
h molecular weight (HMW) DNA fragments by field inversion pulse gel electro
phoresis (FIGE); and (2) morphological characterization of apoptotic cells
after fluorescent staining. In parallel, cell-cycle distribution, monitored
by DNA flow cytometry, as well as measurements of p53/p21(WAF1) protein le
vels by Western blots, were investigated in these cells.
Results: High-LET radiation-induced apoptosis and G2/M-arrest in both A-T a
nd control LCL. No significant increase in the amount of p53/p21(WAF1) prot
eins preceded apoptosis in control or in A-T LCL after high-LET irradiation
. However, low-LET radiation did induce significant enhanced levels of p53
proteins in control but not in A-T LCL.
Conclusions: LCL from both A-T homozygous and unaffected healthy individual
s undergo apoptosis without accumulation of p53/p21(WAF1) proteins after ex
posure to high-LET radiation. In contrast, low-LET radiation induces apopto
sis and significantly increases levels of p53 protein in control but not in
A-T LCL.