Radiation-induced apoptosis varies among individuals and is modified by sex and age

Abstract

Purpose Although there are considerable data on mechanisms of radiation-induced apoptosis in vitro and in animal models, little is known about functional variation in these pathways in humans. We sought to develop a tractable system to evaluate this. Materials and methods Peripheral blood mononuclear cells were isolated from 90 healthy volunteers, divided into two aliquots, one irradiated with a 5 Gy dose and the other sham-treated (0 Gy), and assessed for damage-induced apoptosis after 24 hours. To investigate reproducibility, ten individuals spanning the entire radiation-induced apoptotic range were tested three times each, with 3–6 months between replicates. Results We observed surprising heterogeneity in apoptosis among individuals, ranging from 21–62%. Biological replicates from a single individual, however, were completely concordant, suggesting the variability observed across individuals is not the result of stochastic or short-term effects. We found significantly higher radiation-induced apoptosis in males than in females (Mean: 41.0% vs. 30.7%; p < 3.5 × 10−7). Moreover, advancing age was associated with decreasing radiation-induced apoptosis in males (p = 0.01) but not females (p = 0.82).a Conclusions Our results provide evidence that the function of cellular pathways crucial for stress-induced apoptosis varies by sex and could decline with age in humans.

The Radioprotective Effect of Procaine and Procaine-Derived Product Gerovital H3 in Lymphocytes from Young and Aged Individuals

“…Early studies reported that the survival rate of lymphocytes from elderly individuals after ex vivo irradiation is approximately one-half from that of lymphocytes from young individuals [ 68 ]. Discordantly, a more recent study found an age-associated decrease in IR-induced apoptosis [ 69 ], and this finding was also confirmed in later studies [ 70 , 71 ]. Regarding radiation-induced DNA strand breaks, the number of γ -H2AX foci is higher in young than in old mice, which partially correlated with cellular proliferation and expression of DNA repair proteins [ 72 ].…”

Clinically Relevant Radiation Exposure Differentially Impacts Forms of Cell Death in Human Cells of the Innate and Adaptive Immune System

“…We also identified that B cells of the peripheral blood were less resistant to radiation in comparison to T cells. Future analyses should take into account that cell death responses following radiation exposure might, under distinct microenvironmental conditions, be dependent on age and sex [ 55 ] as well as on the basal inflammatory state [ 7 , 8 ]. Our ex vivo/in vitro studies should also be considered as the first helpful basis to optimize (individualize) radiotherapy in multimodal settings, including for the definition of suited time points for further inclusion of immunotherapies or for reducing the cumulative dose of radiation.…”

Apheresis buffy coat collection without photoactivation has no effect on apoptosis, cell proliferation, and total viability of mononuclear cells collected using photopheresis systems

“…Although this was primarily driven by our risk assessment, we recognize that future studies should be designed to include both sexes. Interestingly, since this study has been completed a study pointing out differences in the rate of apoptosis generated by exposure to irradiation has been published . In this study MNCs derived from females had a lower apoptosis rate (30.7%) than those derived from males (41%).…”