Early G2/M checkpoint failure as a molecular mechanism underlying etoposide-induced chromosomal aberrations
J. Clin. Invest. Shinichiro Nakada, et al. 116:80 doi:10.1172/JCI25716 [
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Figure 4Segregation of etoposide-cleaved DNA ends. (
A and
B) Mock-treated ATM-deficient fibroblasts were hybridized with centromeric (green) and telomeric (red) 11q23 probes. (
A) G1 (a cell with small nucleus with 2 copies of 11q23 signals) and G2 (a cell with large nucleus with 2 sets of replicated 11q23 signals) phase cells. (
B) A metaphase cell. (
C and
D) Segregation of 11q23 segments in 2 μM etoposide–treated ATM-deficient fibroblasts as identified by dissociation of centromeric and telomeric 11q23 signals. (
C) Postmitotic G1 phase cells. (
D) A metaphase cell. Original magnification of FISH images, ×600. The area enclosed by each rectangle is magnified in the bottom row. (
E) Proportion of split 11q23 signal–positive cells in each fraction. All data from 3 independent experiments were combined for the analysis (
n > 450 for each). Vertical lines indicate the 95% confidence intervals. Differences in the proportion of cells with dissociated signals were analyzed by Fisher’s exact test after adjustment for multiple comparisons by the Bonferroni-Holm method (3 comparisons at each drug concentration). *
P < 0.0001.
