The repair of oxidized purines in the DNA of human lymphocytes requires an activation involving NF-YA-mediated upregulation of OGG1

Lippen, Carina von der; Sahu, Sanjeeb Kumar; Seifermann, Marco; Tiwari, Vijay; Epe, Bernd

doi:10.1016/j.dnarep.2014.10.008

Cited by 6 publications

(3 citation statements)

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“…others (Bhattacharya et al, 2009). Secondly, repair systems are more efficient in proliferating lymphocytes used for micronucleus analysis compared to quiescent PBMCs used for the analysis of primary DNA 10.5 ± 6.36 6.5 ± 0.71 6.0 ± 1.41 6.0 ± 1.41 6.5 ± 0.71 50 8.0 ± 2.83 9.5 ± 3.54 5.5 ± 0.71 12.0 ± 4.24* 5.5 ± 0.71 100 9.0 ± 7.07 12.5 ± 7.78 7.0 ± 4.24 9.0 ± 1.41 60.5 ± 0.71 200 9.0 ± 0.00 12.0 ± 0.00 a 7.5 ± 4.95 6.0 ± 0.00 a 10. damage (von der Lippen, Sahu, Seifermann, Tiwari, & Epe, 2015). A third possibility, namely that particle uptake in lymphocytes could be artificially hampered by Cyt B endocytosis inhibition (Gonzalez et al, 2011;Magdolenova et al, 2012), could be discounted based on the negative result of the delayed co-treatment protocol, which allowed 20 hours for NP-cell interaction before the addition of Cyt B. Suzuki, Toyooka, & Ibuki, 2007;Zucker et al, 2010).…”

Section: Flow Cytometrymentioning

confidence: 99%

Critical issues in genotoxicity assessment of TiO₂ nanoparticles by human peripheral blood mononuclear cells

Andreoli

Leter

Berardis

et al. 2018

J of Applied Toxicology

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In the last years, a number of in vitro studies have been performed to assess the genotoxic activity of titanium dioxide (TiO ). To resolve the contradictory results, in this study, we investigated the genotoxic activity of commercial TiO nanoparticles (NPs) and microparticles of different forms (anatase, rutile and mix of both). We evaluated micronucleus formation in stimulated lymphocytes, as well as DNA strand breaks and 8-oxo-7,8-dihydro-2'-deoxyguanosine in peripheral blood mononuclear cells (PBMCs), a mixed population of lymphocytes and monocytes. Different responses to TiO exposure were obtained depending on the assay. Both TiO NPs and microparticles and all the crystalline forms elicited a significant increase in 8-oxo-7,8-dihydro-2'-deoxyguanosine and DNA strand breaks in the whole PBMC population, without a concurrent increase of micronuclei in proliferating lymphocytes. The distribution of DNA damage in PBMCs, detected by the comet assay, that measures DNA damage at level of single cells, indicated the presence of a more susceptible cell subpopulation. The measurement of side scatter signals by flow cytometry highlighted the preferential physical interaction of TiO particles with monocytes that also displayed higher reactive oxygen species generation, providing a mechanistic explanation for the different responses observed in genotoxicity assays with PBMCs and lymphocytes. This study confirmed the suitability of human PBMCs as multi-cell model to investigate NP-induced DNA damage, but suggested some caution in the use of stimulated lymphocytes for the assessment of NP clastogenicity.

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Section: Flow Cytometrymentioning

confidence: 99%

Critical issues in genotoxicity assessment of TiO₂ nanoparticles by human peripheral blood mononuclear cells

Andreoli

Leter

Berardis

et al. 2018

J of Applied Toxicology

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“…The results demonstrated that the expression of OGG1 was upregulated nearly four-fold due to the increased binding of the transcription factor NF-YA and the OGG1 gene promoter. Jun kinase inhibitors can inhibit the binding of OGG1 to NF-YA and the subsequent induction of OGG1 [60], suggesting that human lymphocytes can repair oxidative damage by activating NF-YA to mediate the up-regulation of OGG1 and removal of 8-oxoG (Figure 2). ment of inflammation, the relationship between OGG1 and granulocytes requires further investigation.…”

Section: Ogg1 and Lymphocytesmentioning

confidence: 99%

“…The results demonstrated that the expression of OGG1 was upregulated nearly four-fold due to the increased binding of the transcription factor NF-YA and the OGG1 gene promoter. Jun kinase inhibitors can inhibit the binding of OGG1 to NF-YA and the subsequent induction of OGG1 [60], suggesting that human lymphocytes can repair oxidative damage by activating NF-YA to mediate the upregulation of OGG1 and removal of 8-oxoG (Figure 2). Gautam et al isolated lymphocytes from blood samples of healthy volunteers across different age groups and evaluated the antioxidant status of lymphocytes by detecting lymphocyte lipids and protein damage.…”

Section: Ogg1 and Lymphocytesmentioning

confidence: 99%

Effect of 8-Hydroxyguanine DNA Glycosylase 1 on the Function of Immune Cells

Zhang

Zhong

et al. 2023

Antioxidants

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Excess reactive oxygen species (ROS) can cause an imbalance between oxidation and anti-oxidation, leading to the occurrence of oxidative stress in the body. The most common product of ROS-induced base damage is 8-hydroxyguanine (8-oxoG). Failure to promptly remove 8-oxoG often causes mutations during DNA replication. 8-oxoG is cleared from cells by the 8-oxoG DNA glycosylase 1 (OGG1)-mediated oxidative damage base excision repair pathway so as to prevent cells from suffering dysfunction due to oxidative stress. Physiological immune homeostasis and, in particular, immune cell function are vulnerable to oxidative stress. Evidence suggests that inflammation, aging, cancer, and other diseases are related to an imbalance in immune homeostasis caused by oxidative stress. However, the role of the OGG1-mediated oxidative damage repair pathway in the activation and maintenance of immune cell function is unknown. This review summarizes the current understanding of the effect of OGG1 on immune cell function.

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Mode of action-based risk assessment of genotoxic carcinogens

et al. 2020

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The risk assessment of chemical carcinogens is one major task in toxicology. Even though exposure has been mitigated effectively during the last decades, low levels of carcinogenic substances in food and at the workplace are still present and often not completely avoidable. The distinction between genotoxic and non-genotoxic carcinogens has traditionally been regarded as particularly relevant for risk assessment, with the assumption of the existence of no-effect concentrations (threshold levels) in case of the latter group. In contrast, genotoxic carcinogens, their metabolic precursors and DNA reactive metabolites are considered to represent risk factors at all concentrations since even one or a few DNA lesions may in principle result in mutations and, thus, increase tumour risk. Within the current document, an updated risk evaluation for genotoxic carcinogens is proposed, based on mechanistic knowledge regarding the substance (group) under investigation, and taking into account recent improvements in analytical techniques used to quantify DNA lesions and mutations as well as “omics” approaches. Furthermore, wherever possible and appropriate, special attention is given to the integration of background levels of the same or comparable DNA lesions. Within part A, fundamental considerations highlight the terms hazard and risk with respect to DNA reactivity of genotoxic agents, as compared to non-genotoxic agents. Also, current methodologies used in genetic toxicology as well as in dosimetry of exposure are described. Special focus is given on the elucidation of modes of action (MOA) and on the relation between DNA damage and cancer risk. Part B addresses specific examples of genotoxic carcinogens, including those humans are exposed to exogenously and endogenously, such as formaldehyde, acetaldehyde and the corresponding alcohols as well as some alkylating agents, ethylene oxide, and acrylamide, but also examples resulting from exogenous sources like aflatoxin B1, allylalkoxybenzenes, 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), benzo[a]pyrene and pyrrolizidine alkaloids. Additionally, special attention is given to some carcinogenic metal compounds, which are considered indirect genotoxins, by accelerating mutagenicity via interactions with the cellular response to DNA damage even at low exposure conditions. Part C finally encompasses conclusions and perspectives, suggesting a refined strategy for the assessment of the carcinogenic risk associated with an exposure to genotoxic compounds and addressing research needs.

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The repair of oxidized purines in the DNA of human lymphocytes requires an activation involving NF-YA-mediated upregulation of OGG1

Cited by 6 publications

References 50 publications

Critical issues in genotoxicity assessment of TiO₂ nanoparticles by human peripheral blood mononuclear cells

Critical issues in genotoxicity assessment of TiO₂ nanoparticles by human peripheral blood mononuclear cells

Effect of 8-Hydroxyguanine DNA Glycosylase 1 on the Function of Immune Cells

Mode of action-based risk assessment of genotoxic carcinogens

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The repair of oxidized purines in the DNA of human lymphocytes requires an activation involving NF-YA-mediated upregulation of OGG1

Cited by 6 publications

References 50 publications

Critical issues in genotoxicity assessment of TiO2 nanoparticles by human peripheral blood mononuclear cells

Critical issues in genotoxicity assessment of TiO2 nanoparticles by human peripheral blood mononuclear cells

Effect of 8-Hydroxyguanine DNA Glycosylase 1 on the Function of Immune Cells

Mode of action-based risk assessment of genotoxic carcinogens

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Critical issues in genotoxicity assessment of TiO₂ nanoparticles by human peripheral blood mononuclear cells

Critical issues in genotoxicity assessment of TiO₂ nanoparticles by human peripheral blood mononuclear cells