The senescence induced by ionizing radiation is a very important radiobiological effect. It causes inhibition of cell growth and reduction of cellular function. In our previous work, we found that radiation-induced senescence was related to the long-term arrest of G1 and G2 phase in a human uveal melanoma cell line 92-1. Diploid cells undergoing senescence and mitotic slippage have been reported in literature, however, the mechanism of tretraploid cells undergoing senescence remains unclear. In this study, we illustrated that tretraploid cells which corresponding to long-term G2-arrested cells underwent senescence by G2 slippage. Besides the senescent diploid cells, significant proportion of senescent tretraploid cells was observed after irradiation.
The genes essential for G2-M transition were prematurely downregulated at both transcriptional and translational levels. It was deduced that the long-term G2-arrested cells slipped into G1 phase directly, and underwent senescence along with the long-term G1 arrested cells together. This was confirmed by the expression levels of the G1-specific markers, Cyclin D1 and Caveolin-1 which were distinctly increased, and by S/G2-specific markers, Cyclin B1 and Aurora A which were significantly downregulated. This deep understanding of how long-term G2 arrested cells undergoing senescence will probably enrich our insights into the mechanisms that link DNA damage and aging after irradiation.