The mechanism of radiation-induced senescence and the effect for angiogenesis in endothelial cells

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The effects of ionizing radiation (IR) on tumor angiogenesis still remain largely unknown. In this study, we found that IR (8 Gy) induces a high frequency (80-90%) senescence-like phenotype in vascular endothelial cells (ECs) undergoing exponential growth. This finding allowed us to characterize the IR-induced senescence-like (IRSL) phenotype by examining the gene expression profiles and in vitro angiogenic activities of these ECs. Expression of genes associated with cell cycle progression and DNA replication was remarkably decreased and in vitro invasion and migration activities through Matrigel of these IRSL ECs were significantly suppressed. We also found that confluent ECs exhibited a high frequency IRSL phenotype when replated immediately after irradiation, but incubation in plateau-phase conditions reduced induction of the phenotype and enhanced cell survival as determined by colony formation. DNA double strand breaks (DSB) repair kinetics showed a faster time course in confluent Ecs than in growing Ecs, which may contribute to the protective mechanism of the IRSL phenotype in the former. These results imply that the IRSL phenotype could be an important factor for determining the angiogenic activity of Ecs following irradiation. The present study should shed additional light on understanding the effect of IR on tumor angiogenesis.