Does low dose radiation induced adaptive response influence initial DNA-DSB formation? Evidence from γH2AX foci analysis in human lymphocytes.

PURPOSE: Low-dose radiation-induced adaptive response (LDRIAR) is well documented, but its role in early DNA damage signaling remains unclear. This study aimed to investigate whether adaptive response influences initial DNA double-strand break (DSB) recognition, as reflected by γH2AX foci formation, and to evaluate its time-dependent expression in human lymphocytes. MATERIALS AND METHODS: Peripheral blood lymphocytes from three healthy donors were exposed to a priming dose followed by a challenging dose at defined time intervals. DNA damage was assessed using γH2AX foci analysis, comparing acute and split-dose exposures in both PHA-stimulated (large) and non-stimulated (small) lymphocytes. RESULTS: A clear time-dependent adaptive response was observed. No significant reduction in γH2AX foci was detected at 1 h (p > 0.05). At 2 h, a significant decrease was observed (∼7-8% in large and ∼13% in small lymphocytes; p < 0.01), which increased at 4 h (∼12% and ∼22%, respectively; p < 0.001). The maximal response occurred at 15 h, with reductions of ∼40-43% in large and ∼27% in small lymphocytes (p < 0.001). Small lymphocytes exhibited an earlier response, while large lymphocytes showed a greater magnitude at later time points. The temporal trend was consistent across donors, with minor variability at later intervals. CONCLUSIONS: The findings demonstrate that LDRIAR is reflected at the level of DNA damage signaling and follows a defined temporal pattern with cell-type specificity. This suggests that adaptive response may influence early DSB-associated processes, contributing to a better understanding of radiation response mechanisms in radiobiology.