HU neither requires functional ATM, nor interferes with the γ
IR-dependent activation of ATM kinase. (A) HCT116 cells
were pretreated with wortmannin in DMSO (W; lanes 4 and 7, 20 μM;
lanes 2, 5 and 8, 50 μM) or DMSO (lanes 1, 3, and 6) for 2 h,
then either exposed to γ IR (10 Gy) or HU (1.5 mM) for 6 h, and
cell extracts were analyzed by Western blotting using either PAb 1801
(p53) or phospho-serine 15-specific antibodies (pS15). Actin was used
as a loading control. NT, not treated. (B) Normal and
AT−/− lymphoblasts were untreated (−) or treated with γ IR (3.5
Gy). Cells were harvested at the indicated hours after treatment, and
lysates from each sample were analyzed as described in
A. (C) Normal and AT−/− lymphoblasts
were either untreated (−) or treated with HU (1.5 mM). Cells were
harvested at the indicated hours and analyzed as in A.
(D) SAOS-2 cells were grown without treatment (−) or
exposed to HU treatment for 13 h (HU and HU + γ) or subjected to
γ IR for 1 h (HU+ γ and γ). All samples were treated with
MG132 proteosome inhibitor for 2 h before lysis to allow HDM-2
accumulation. Total cellular extracts were immunoblotted with the two
indicated mAbs to HDM-2. Actin was used as a normalization control.