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.
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.
Entities:
Keywords:
Ionizing radiation; age; apoptosis; human cells; models of cell killing
Authors: Bert Gold; Francis Kalush; Julie Bergeron; Kevin Scott; Nandita Mitra; Kelly Wilson; Nathan Ellis; Helen Huang; Michael Chen; Ross Lippert; Bjarni V Halldorsson; Beth Woodworth; Thomas White; Andrew G Clark; Fritz F Parl; Samuel Broder; Michael Dean; Kenneth Offit Journal: Cancer Res Date: 2004-12-15 Impact factor: 12.701
Authors: Gareth L Bond; Kim M Hirshfield; Tomas Kirchhoff; Gabriella Alexe; Elisabeth E Bond; Harlan Robins; Frank Bartel; Helge Taubert; Peter Wuerl; William Hait; Deborah Toppmeyer; Kenneth Offit; Arnold J Levine Journal: Cancer Res Date: 2006-05-15 Impact factor: 12.701
Authors: Gareth L Bond; Wenwei Hu; Elisabeth E Bond; Harlan Robins; Stuart G Lutzker; Nicoleta C Arva; Jill Bargonetti; Frank Bartel; Helge Taubert; Peter Wuerl; Kenan Onel; Linwah Yip; Shih-Jen Hwang; Louise C Strong; Guillermina Lozano; Arnold J Levine Journal: Cell Date: 2004-11-24 Impact factor: 41.582
Authors: M Utsuyama; K Hirokawa; C Kurashima; M Fukayama; T Inamatsu; K Suzuki; W Hashimoto; K Sato Journal: Mech Ageing Dev Date: 1992-03-15 Impact factor: 5.432
Authors: Helen Budworth; Antoine M Snijders; Francesco Marchetti; Brandon Mannion; Sandhya Bhatnagar; Ely Kwoh; Yuande Tan; Shan X Wang; William F Blakely; Matthew Coleman; Leif Peterson; Andrew J Wyrobek Journal: PLoS One Date: 2012-11-07 Impact factor: 3.240
Authors: Sylvia E Falcke; Paul F Rühle; Lisa Deloch; Rainer Fietkau; Benjamin Frey; Udo S Gaipl Journal: Int J Mol Sci Date: 2018-11-13 Impact factor: 5.923