Donor-Specific Cell-Based Assays in Studying Sensitivity to Low-Dose Radiation: A Population-Based Perspective

Il’yasova, Dora; Kinev, Alexander; Melton, Charlie; Davis, Faith G.

doi:10.3389/fpubh.2014.00244

Cited by 6 publications

(4 citation statements)

References 67 publications

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“…Dicentric chromosomes without accompanying fragments and pericentric inversions were also detected, both representing long-lived chromosome aberrations from past exposure ( 21 , 22 ). Numerous studies support our findings of increased rate of chromosome aberrations and high interindividual variability ( 23 , 24 , 25 ), which is attributed to differences in genetic susceptibility towards ionising radiation ( 26 , 27 , 28 , 29 , 30 , 31 , 32 ), activation of DNA repair ( 33 , 34 ), and anti-inflammatory processes ( 35 ). Lymphocyte chromosome aberrations in our occupationally exposed participants whose annual doses did not exceed risk limits can also be attributed to cumulative effects of chronic exposure to low-dose ionising radiation ( 36 ).…”

Section: Resultssupporting

confidence: 87%

Telomere fragility in radiology workers occupationally exposed to low doses of ionising radiation

Tričković

Šobot

Joksić³

et al. 2022

Archives of Industrial Hygiene and Toxicology

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Ionising radiation damages DNA directly and indirectly through increased production of reactive oxygen species. Although telomeres have been reported as indicators of radiosensitivity, their maintenance in response to occupational exposure to low radiation doses is still a matter of debate. In this work we aimed to investigate telomere length and structure in hospital workers occupationally exposed to X-rays and to relate these findings to oxidation of biomolecules and chromosome aberrations. Blood samples of exposed participants and matching controls were taken during periodical check-ups. Chromosome aberrations and telomere length and structure were analysed in peripheral blood lymphocytes using Q-FISH, whereas oxidative stress parameters [pro/antioxidant balance (PAB), lipid peroxidation, and 8-oxo-dG] were measured in plasma samples. Based on the CA findings we divided the exposed group into two subgroups, of which one had chromosome aberrations in the first division metaphases and the other did not. There was no significant difference in telomere length between any of the groups. However, both subgroups showed significantly higher rate of fragile telomeres and higher lipid peroxidation product and 8-oxo-dG levels than controls. The rate of fragile telomeres significantly correlated with plasma levels of 8-oxo-dG, which suggests that continuous exposure to low radiation doses induces oxidative base damage of guanine resulting in telomere fragility.

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Section: Resultssupporting

confidence: 87%

Telomere fragility in radiology workers occupationally exposed to low doses of ionising radiation

Tričković

Šobot

Joksić³

et al. 2022

Archives of Industrial Hygiene and Toxicology

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“…The measurement of F2-IsoP in biological fluids, as well as in the condensation of the breath, can provide an estimate of the systemic oxidative stress, while the measurement of esterified F2-IsoP in specific tissues can quantify a circumscribed oxidative stress. The most reliable methods for their quantification, the gas/liquid chromatography coupled with the mass spectroscopy techniques (HPLC/GC-MS), are laborious and require specialized and expensive instrumentation [ 104 ], while commercial immunoassays are often less reliable [ 105 ].…”

Section: Available Methods To Assess Oxidative Stress In Clinical mentioning

confidence: 99%

The Impact of Oxidative Stress in Human Pathology: Focus on Gastrointestinal Disorders

et al. 2021

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Accumulating evidence shows that oxidative stress plays an essential role in the pathogenesis and progression of many diseases. The imbalance between the production of reactive oxygen species (ROS) and the antioxidant systems has been extensively studied in pulmonary, neurodegenerative cardiovascular disorders; however, its contribution is still debated in gastrointestinal disorders. Evidence suggests that oxidative stress affects gastrointestinal motility in obesity, and post-infectious disorders by favoring the smooth muscle phenotypic switch toward a synthetic phenotype. The aim of this review is to gain insight into the role played by oxidative stress in gastrointestinal pathologies (GIT), and the involvement of ROS in the signaling underlying the muscular alterations of the gastrointestinal tract (GIT). In addition, potential therapeutic strategies based on the use of antioxidants for the treatment of inflammatory gastrointestinal diseases are reviewed and discussed. Although substantial progress has been made in identifying new techniques capable of assessing the presence of oxidative stress in humans, the biochemical-molecular mechanisms underlying GIT mucosal disorders are not yet well defined. Therefore, further studies are needed to clarify the mechanisms through which oxidative stress-related signaling can contribute to the alteration of the GIT mucosa in order to devise effective preventive and curative therapeutic strategies

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“…Numerous studies have been conducted demonstrating individual variability using primary cells. For instance, umbilical cord blood-derived cells were exploited to examine individual variability in the proliferative response to low-dose radiations ( 133 , 134 ). Primary human B lymphocytes from different donors were utilized to characterize the inter-individual variability in the immunotoxic effect of dioxin on the antibody secretion response and to ascertain how the variability may affect the linearization of the population-average dose response curves ( 21 ).…”

Section: Computational Approaches For Dose-response and Extrapolationmentioning

confidence: 99%

Bridging the Data Gap From in vitro Toxicity Testing to Chemical Safety Assessment Through Computational Modeling

Zhang

Jin

Middleton

et al. 2018

Front. Public Health

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Chemical toxicity testing is moving steadily toward a human cell and organoid-based in vitro approach for reasons including scientific relevancy, efficiency, cost, and ethical rightfulness. Inferring human health risk from chemical exposure based on in vitro testing data is a challenging task, facing various data gaps along the way. This review identifies these gaps and makes a case for the in silico approach of computational dose-response and extrapolation modeling to address many of the challenges. Mathematical models that can mechanistically describe chemical toxicokinetics (TK) and toxicodynamics (TD), for both in vitro and in vivo conditions, are the founding pieces in this regard. Identifying toxicity pathways and in vitro point of departure (PoD) associated with adverse health outcomes requires an understanding of the molecular key events in the interacting transcriptome, proteome, and metabolome. Such an understanding will in turn help determine the sets of sensitive biomarkers to be measured in vitro and the scope of toxicity pathways to be modeled in silico. In vitro data reporting both pathway perturbation and chemical biokinetics in the culture medium serve to calibrate the toxicity pathway and virtual tissue models, which can then help predict PoDs in response to chemical dosimetry experienced by cells in vivo. Two types of in vitro to in vivo extrapolation (IVIVE) are needed. (1) For toxic effects involving systemic regulations, such as endocrine disruption, organism-level adverse outcome pathway (AOP) models are needed to extrapolate in vitro toxicity pathway perturbation to in vivo PoD. (2) Physiologically-based toxicokinetic (PBTK) modeling is needed to extrapolate in vitro PoD dose metrics into external doses for expected exposure scenarios. Linked PBTK and TD models can explore the parameter space to recapitulate human population variability in response to chemical insults. While challenges remain for applying these modeling tools to support in vitro toxicity testing, they open the door toward population-stratified and personalized risk assessment.

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Donor-Specific Cell-Based Assays in Studying Sensitivity to Low-Dose Radiation: A Population-Based Perspective

Cited by 6 publications

References 67 publications

Telomere fragility in radiology workers occupationally exposed to low doses of ionising radiation

Telomere fragility in radiology workers occupationally exposed to low doses of ionising radiation

The Impact of Oxidative Stress in Human Pathology: Focus on Gastrointestinal Disorders

Bridging the Data Gap From in vitro Toxicity Testing to Chemical Safety Assessment Through Computational Modeling

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