title: Radiation-induced apoptosis varies among individuals and is modified by sex and age.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Pediatrics, The University of Chicago , Chicago, Illinois , USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Applebaum
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Skol
authors.forename: Elisabeth E
authors.initials: EE
authors.lastname: Bond
authors.forename: Michael
authors.initials: M
authors.lastname: Overholtzer
authors.forename: Gareth L
authors.initials: GL
authors.lastname: Bond
authors.forename: Kenan
authors.initials: K
authors.lastname: Onel
mesh_terms: D000328:Adult; D000375:Aging / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects*; D002478:Cells, Cultured; D003198:Computer Simulation; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011829:Radiation Dosage; D012016:Reference Values; D012737:Sex Factors; D055815:Young Adult
keywords: Ionizing radiation; age; apoptosis; human cells; models of cell killing