Mouse Embryonic Stem Cells that Survive gamma-Rays Exposure Maintain Pluripotent Differentiation Potential and Genome Stability

This study aimed to investigate the cell cycle, apoptosis, cytogenetics and differentiation capacity of mouse embryonic stem cells (mESCs) that survived a single dose of 2 or 5Gy -rays during a period of up to 96h of culture. After 2Gy irradiation and 24h culture, compared to control, a significant majority of cells was blocked at the G2/M phase and a massive apoptosis was recorded. Between 48 and 72h post-irradiation, the parameters used to describe the cell cycle and apoptosis returned similar to those of control samples. When mESCs were irradiated with 5Gy, a small fraction of cells, even after 96h of culture, still presented clear evidences of a G2/M block and apoptosis. The cytogenetic analysis performed at 96h showed that the structural stability of the aberrations did not change significantly when comparing control and 2 or 5Gy-treated populations. However, the chromosomal damage observed in the progeny of the survived cells after 5Gy exposure is significantly higher than that observed in control samples, although it is mostly of the stable and transmissible type. Ninety-six hours after irradiation, the survived mESCs maintained their undifferentiated status and capability to differentiate into the three germ layers. Overall, these results indicate a commitment of mESCs to maintain pluripotency and genome stability.