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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, 10 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). 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.

Original publication

DOI

10.3109/09553002.2014.925603

Type

Journal article

Journal

Int J Radiat Biol

Publication Date

10/2014

Volume

90

Pages

903 - 908

Keywords

Ionizing radiation, age, apoptosis, human cells, models of cell killing, Adult, Aging, Apoptosis, Cells, Cultured, Computer Simulation, Female, Humans, Leukocytes, Mononuclear, Male, Middle Aged, Models, Biological, Radiation Dosage, Reference Values, Sex Factors, Young Adult