Photon versus proton neurotoxicity: Impact on mitochondrial function and 8-OHdG base-excision repair mechanism in human astrocytes
| Autor: | Chukwumaobim D. Nwokwu, Gergana G. Nestorova, Kristen H. Hutson, Kaitlynn Willis, Matthew Maynard |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Senescence
Mitochondrial DNA DNA Repair DNA repair Enzyme-Linked Immunosorbent Assay Toxicology medicine.disease_cause 03 medical and health sciences Oxygen Consumption 0302 clinical medicine DNA Repair Protein medicine Humans Cells Cultured 030304 developmental biology Photons 0303 health sciences Chemistry General Neuroscience Base excision repair medicine.disease Molecular biology Mitochondria Nuclear DNA Astrogliosis 8-Hydroxy-2'-Deoxyguanosine Astrocytes Protons Transcriptome Oxidation-Reduction 030217 neurology & neurosurgery Oxidative stress |
| Zdroj: | NeuroToxicology. 82:158-166 |
| ISSN: | 0161-813X |
| DOI: | 10.1016/j.neuro.2020.12.011 |
| Popis: | This study assesses and compares the neurotoxic effects of proton and photon radiation on mitochondrial function and DNA repair capabilities of human astrocytes. Human astrocytes received either proton (0.5 Gy and 3 Gy), photon (0.5 Gy and 3 Gy), or sham-radiation treatment. The mRNA expression level of the DNA repair protein OGG1 was determined via RT-qPCR. The levels of 8-OHdG in the cell media were measured via ELISA. Real-time kinetic analysis of extracellular oxygen consumption rates was performed to assess mitochondrial function. Radiation-induced changes in mitochondrial mass and oxidative activity were assessed using fluorescent imaging with MitoTracker™ Green FM and MitoTracker™ Orange CM-H2TMRos dyes respectively. PCR was used to quantify the alteration in the mitochondrial DNA content, measured as the mitochondrial to nuclear DNA ratio. A significant increase in mitochondrial mass and levels of reactive oxygen species was observed after radiation treatment. Additionally, real-time PCR analysis indicated a significant depletion of mitochondrial DNA content in the irradiated cells when compared to the control. This was accompanied by a decreased gene expression of the DNA base-excision repair protein OGG1 and reduced clearance of 8-OHdG adducts from the genome. Photon radiation treatment was associated with a more detrimental cellular impact when compared to the same dose of proton radiation. These results are indicative of a radiation-induced dose-dependent decrease in mitochondrial function, an increase in senescence and astrogliosis, and impairment of the DNA repair capabilities in healthy glial cells. Photon irradiation was associated with a more significant disruption in mitochondrial function and base-excision repair mechanisms in vitro in comparison to proton treatment. |
| Databáze: | OpenAIRE |
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