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Functional consequences of radiation-induced oxidative stress in cultured neural stem cells and the brain exposed to charged particle irradiation.

ABSTRACT: Redox homeostasis is critical in regulating the fate and function of multipotent cells in the central nervous system (CNS). Here, we investigated whether low dose charged particle irradiation could elicit oxidative stress in neural stem and precursor cells and whether radiation-induced changes in redox metabolism would coincide with cognitive impairment.Low doses (<1 Gy) of charged particles caused an acute and persistent oxidative stress. Early after (<1 week) irradiation, increased levels of reactive oxygen and nitrogen species were generally dose responsive, but were less dependent on dose weeks to months thereafter. Exposure to ion fluences resulting in less than one ion traversal per cell was sufficient to elicit radiation-induced oxidative stress. Whole body irradiation triggered a compensatory response in the rodent brain that led to a significant increase in antioxidant capacity 2 weeks following exposure, before returning to background levels at week 4. Low dose irradiation was also found to significantly impair novel object recognition in mice 2 and 12 weeks following irradiation.Data provide evidence that acute exposure of neural stem cells and the CNS to very low doses and fluences of charged particles can elicit a persisting oxidative stress lasting weeks to months that is associated with impaired cognition.Exposure to low doses of charged particles causes a persistent oxidative stress and cognitive impairment over protracted times. Data suggest that astronauts subjected to space radiation may develop a heightened risk for mission critical performance decrements in space, along with a risk of developing long-term neurocognitive sequelae.

SUBMITTER: Tseng BP

PROVIDER: S-EPMC3936501 | biostudies-other | 2014 Mar

REPOSITORIES: biostudies-other

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Functional consequences of radiation-induced oxidative stress in cultured neural stem cells and the brain exposed to charged particle irradiation.

Tseng Bertrand P BP Giedzinski Erich E Izadi Atefeh A Suarez Tatiana T Lan Mary L ML Tran Katherine K KK Acharya Munjal M MM Nelson Gregory A GA Raber Jacob J Parihar Vipan K VK Limoli Charles L CL

Antioxidants & redox signaling 20130812 9

<h4>Aims</h4>Redox homeostasis is critical in regulating the fate and function of multipotent cells in the central nervous system (CNS). Here, we investigated whether low dose charged particle irradiation could elicit oxidative stress in neural stem and precursor cells and whether radiation-induced changes in redox metabolism would coincide with cognitive impairment.<h4>Results</h4>Low doses (<1 Gy) of charged particles caused an acute and persistent oxidative stress. Early after (<1 week) irrad ...[more]

PMID: 23802883

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Project description:PurposeGiven the higher precision accompanied by optimized sparing of normal tissue, charged particle therapy was thought of as a promising treatment for pancreatic cancer. However, systematic preclinical studies were scarce. We aimed to investigate the radiobiological effects of charged particle irradiation on pancreatic cancer cell lines.MethodsA systematic literature search was performed in EMBASE (OVID), Medline (OVID), and Web of Science databases. Included studies were in vitro English publications that reported the radiobiological effects of charged particle irradiation on pancreatic cancer cells.ResultsThirteen carbon ion irradiation and seven proton irradiation in vitro studies were included finally. Relative biological effectiveness (RBE) values of carbon ion irradiation and proton irradiation in different human pancreatic cancer cell lines ranged from 1.29 to 4.5, and 0.6 to 2.1, respectively. The mean of the surviving fraction of 2 Gy (SF2) of carbon ion, proton, and photon irradiation was 0.18 ± 0.11, 0.48 ± 0.11, and 0.57 ± 0.13, respectively. Carbon ion irradiation induced more G2/M arrest and a longer-lasting expression of γH2AX than photon irradiation. Combination therapies enhanced the therapeutic effects of pancreatic cell lines with a mean standard enhancement ratio (SER) of 1.66 ± 0.63 for carbon ion irradiation, 1.55 ± 0.27 for proton irradiation, and 1.52 ± 0.30 for photon irradiation. Carbon ion irradiation was more effective in suppressing the migration and invasion than photon irradiation, except for the PANC-1 cells.ConclusionsCurrent in vitro evidence demonstrates that, compared with photon irradiation, carbon ion irradiation offers superior radiobiological effects in the treatment of pancreatic cancer. Mechanistically, high-LET irradiation may induce complex DNA damage and ultimately promote genomic instability and cell death. Both carbon ion irradiation and proton irradiation confer similar sensitization effects in comparison with photon irradiation when combined with chemotherapy or targeted therapy.

Project description:BackgroundThe radiation-induced "bystander effect" (RIBE) was shown to occur in a number of experimental systems both in vitro and in vivo as a result of exposure to ionizing radiation (IR). RIBE manifests itself by intercellular communication from irradiated cells to non-irradiated cells which may cause DNA damage and eventual death in these bystander cells. It is known that human stem cells (hSC) are ultimately involved in numerous crucial biological processes such as embryologic development; maintenance of normal homeostasis; aging; and aging-related pathologies such as cancerogenesis and other diseases. However, very little is known about radiation-induced bystander effect in hSC. To mechanistically interrogate RIBE responses and to gain novel insights into RIBE specifically in hSC compartment, both medium transfer and cell co-culture bystander protocols were employed.Methodology/principal findingsHuman bone-marrow mesenchymal stem cells (hMSC) and embryonic stem cells (hESC) were irradiated with doses 0.2 Gy, 2 Gy and 10 Gy of X-rays, allowed to recover either for 1 hr or 24 hr. Then conditioned medium was collected and transferred to non-irradiated hSC for time course studies. In addition, irradiated hMSC were labeled with a vital CMRA dye and co-cultured with non-irradiated bystander hMSC. The medium transfer data showed no evidence for RIBE either in hMSC and hESC by the criteria of induction of DNA damage and for apoptotic cell death compared to non-irradiated cells (p>0.05). A lack of robust RIBE was also demonstrated in hMSC co-cultured with irradiated cells (p>0.05).Conclusions/significanceThese data indicate that hSC might not be susceptible to damaging effects of RIBE signaling compared to differentiated adult human somatic cells as shown previously. This finding could have profound implications in a field of radiation biology/oncology, in evaluating radiation risk of IR exposures, and for the safety and efficacy of hSC regenerative-based therapies.

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Functional consequences of radiation-induced oxidative stress in cultured neural stem cells and the brain exposed to charged particle irradiation.

Publications

Functional consequences of radiation-induced oxidative stress in cultured neural stem cells and the brain exposed to charged particle irradiation.

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