Residual γH2AX foci induced by low dose x-ray radiation in bone marrow mesenchymal stem cells do not cause accelerated senescence in the progeny of irradiated cells

Mechanisms underlying the effects of low-dose ionizing radiation (IR) exposure (10-100 mGy) remain unknown. Here we present a comparative study of early (less than 24h) and delayed (up to 11 post-irradiation passages) radiation effects caused by low (80 mGy) vs intermediate (1000 mGy) dose X-ray exposure in cultured human bone marrow mesenchymal stem cells (MSCs). We show that γH2AX foci induced by an intermediate dose returned back to the control value by 24 h post-irradiation. In contrast, low-dose irradiation resulted in residual γH2AX foci still present at 24 h. Notably, these low dose induced residual γH2AX foci were not co-localized with ρATM foci and were observed predominantly in the proliferating Ki67 positive (Ki67+) cells. The number of γH2AX foci and the fraction of nonproliferating (Ki67-) and senescent (SA-β-gal+) cells measured at passage 11 were increased in cultures exposed to an intermediate dose compared to unirradiated controls. These delayed effects were not seen in the progeny of cells that were irradiated with low-dose X-rays, although such exposure resulted in residual γH2AX foci in directly irradiated cells. Taken together, our results support the hypothesis that the low-dose IR induced residual γH2AX foci do not play a role in delayed irradiation consequences, associated with cellular senescence in cultured MSCs.