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Impact of the redox environment on propagation of radiation bystander effects: The modulating effect of oxidative metabolism and oxygen partial pressure.
- Source :
-
Mutation research. Genetic toxicology and environmental mutagenesis [Mutat Res Genet Toxicol Environ Mutagen] 2022 Nov-Dec; Vol. 883-884, pp. 503559. Date of Electronic Publication: 2022 Nov 14. - Publication Year :
- 2022
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Abstract
- Redox modulated pathways play important roles in out-of-field effects of ionizing radiation. We investigated how the redox environment impacts the magnitude of propagation of stressful effects from irradiated to bystander cells. Normal human fibroblasts that have incorporated [ <superscript>3</superscript> H]-thymidine were intimately co-cultured with bystander cells in a strategy that allowed isolation of bystander cells with high purity. The antioxidant glutathione peroxidase (GPX) was maintained either at wild-type conditions or overexpressed in the bystanders. Following 24 h of coculture, levels of stress-responsive p21 <superscript>Waf1</superscript> , p-Hdm2, and connexin43 proteins were increased in bystander cells expressing wild-type GPX relative to respective controls. These levels were significantly attenuated when GPX was ectopically overexpressed, demonstrating by direct approach the involvement of a regulator of intracellular redox homeostasis. Evidence of participation of pro-oxidant compounds was generated by exposing confluent cell cultures to low fluences of 3.7 MeV α particles in presence or absence of t-butyl hydroperoxide. By 3 h post-exposure to fluences wherein only ∼2% of cells are traversed through the nucleus by a particle track, increases in chromosomal damage were greater than expected in absence of the drug (p < 0.001) and further enhanced in its presence (p < 0.05). While maintenance and irradiation of cell cultures at low oxygen pressure (pO <subscript>2</subscript> 3.8 mm Hg) to mimic in vivo still supported the participation of bystander cells in responses assessed by chromosomal damage and stress-responsive protein levels (p < 0.001), the effects were attenuated compared to ambient pO <subscript>2</subscript> (155 mm Hg) (p < 0.05). Together, the results show that bystander effects are attenuated at below ambient pO <subscript>2</subscript> and when metabolic oxidative stress is reduced but increased when the basal redox environment tilts towards oxidizing conditions. They are consistent with bystander effects being independent of radiation dose rate.<br />Competing Interests: Declaration of Competing Interest The authors report no conflict of interest.<br /> (Copyright © 2022 Elsevier B.V. All rights reserved.)
- Subjects :
- Humans
Glutathione Peroxidase metabolism
Partial Pressure
Coculture Techniques
Bystander Effect radiation effects
Oxidation-Reduction radiation effects
Oxidative Stress radiation effects
Radiation Exposure adverse effects
Oxygen adverse effects
Oxygen analysis
Fibroblasts drug effects
Fibroblasts metabolism
Fibroblasts radiation effects
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3592
- Volume :
- 883-884
- Database :
- MEDLINE
- Journal :
- Mutation research. Genetic toxicology and environmental mutagenesis
- Publication Type :
- Academic Journal
- Accession number :
- 36462795
- Full Text :
- https://doi.org/10.1016/j.mrgentox.2022.503559