Abstract
X-ray-induced senescence-like growth arrest (SLGA) gives some similar phenotypes to senescent cells, which are flattened morphology, expression of senescence-associated-&beta-galactosidase (SA-&beta-gal) and p53-dependent irreversible G1-arrest. Although it has been thought that residual DNA double strand breaks induce SLGA, the causal relation is not clear. In this report, we investigated localization of X-rays induced phosphorylated histone H2AX in mitotic cells to examine if residual DNA double strand breaks are involved in SLGA induction.
In response to 4 Gy of X-rays, 40 % of normal human diploid cells became SA-&beta-gal positive 4 days after irradiation, and approximately 80 % of cells showed phosphorylated H2AX foci (within 5 foci per nucleus). We found that all foci colocalized with phosphorylated ATM foci. In metaphase cells, phosphorylated H2AX foci were observed on chromosome fragment, but in addition, they were detected on chromosomes without any detectable aberration. Furthermore, phosphorylated H2AX foci were located on 80 % of observed chromosomal bridge, which results from illegitimated DNA-rejoining. These results indicate that not only DNA double strand breaks but also altered chromatin structure are associated with SLGA induction.
