scholarly journals High-LET Carbon and Iron Ions Elicit a Prolonged and Amplified p53 Signaling and Inflammatory Response Compared to low-LET X-Rays in Human Peripheral Blood Mononuclear Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Ellina Macaeva ◽  
Kevin Tabury ◽  
Arlette Michaux ◽  
Ann Janssen ◽  
Nicole Averbeck ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Heavy Ions ◽  
Mononuclear Cells ◽  
X Rays ◽  
Iron Ions ◽  
Carbon Ions ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Radiation Type

Understanding the differences in biological response to photon and particle radiation is important for optimal exploitation of particle therapy for cancer patients, as well as for the adequate application of radiation protection measures for astronauts. To address this need, we compared the transcriptional profiles of isolated peripheral blood mononuclear cells 8 h after exposure to 1 Gy of X-rays, carbon ions or iron ions with those of non-irradiated cells using microarray technology. All genes that were found differentially expressed in response to either radiation type were up-regulated and predominantly controlled by p53. Quantitative PCR of selected genes revealed a significantly higher up-regulation 24 h after exposure to heavy ions as compared to X-rays, indicating their prolonged activation. This coincided with increased residual DNA damage as evidenced by quantitative γH2AX foci analysis. Furthermore, despite the converging p53 signature between radiation types, specific gene sets related to the immune response were significantly enriched in up-regulated genes following irradiation with heavy ions. In addition, irradiation, and in particular exposure to carbon ions, promoted transcript variation. Differences in basal and iron ion exposure-induced expression of DNA repair genes allowed the identification of a donor with distinct DNA repair profile. This suggests that gene signatures may serve as a sensitive indicator of individual DNA damage repair capacity. In conclusion, we have shown that photon and particle irradiation induce similar transcriptional pathways, albeit with variable amplitude and timing, but also elicit radiation type-specific responses that may have implications for cancer progression and treatment

DNA Damage and Decreased DNA Repair in Peripheral Blood Mononuclear Cells in Individuals Exposed to Arsenic and Lead in a Mining Site

2011 ◽  
Vol 146 (2) ◽  
pp. 141-149 ◽  
Author(s):  
Yolanda Jasso-Pineda ◽  
Fernando Díaz-Barriga ◽  
Jaqueline Calderón ◽  
Leticia Yáñez ◽  
Leticia Carrizales ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Mining Site ◽  
Blood Mononuclear Cells

scholarly journals α-Particle-induced DNA damage tracks in peripheral blood mononuclear cells of [223Ra]RaCl2-treated prostate cancer patients

2021 ◽  
Author(s):  
S. Schumann ◽  
U. Eberlein ◽  
C. Lapa ◽  
J. Müller ◽  
S. Serfling ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Damage ◽  
Cancer Patients ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Absorbed Dose ◽  
Peripheral Blood Mononuclear ◽  
Absorbed Doses ◽  
Blood Mononuclear Cells

Abstract Purpose One therapy option for prostate cancer patients with bone metastases is the use of [223Ra]RaCl2. The α-emitter 223Ra creates DNA damage tracks along α-particle trajectories (α-tracks) in exposed cells that can be revealed by immunofluorescent staining of γ-H2AX+53BP1 DNA double-strand break markers. We investigated the time- and absorbed dose-dependency of the number of α-tracks in peripheral blood mononuclear cells (PBMCs) of patients undergoing their first therapy with [223Ra]RaCl2. Methods Multiple blood samples from nine prostate cancer patients were collected before and after administration of [223Ra]RaCl2, up to 4 weeks after treatment. γ-H2AX- and 53BP1-positive α-tracks were microscopically quantified in isolated and immuno-stained PBMCs. Results The absorbed doses to the blood were less than 6 mGy up to 4 h after administration and maximally 16 mGy in total. Up to 4 h after administration, the α-track frequency was significantly increased relative to baseline and correlated with the absorbed dose to the blood in the dose range < 3 mGy. In most of the late samples (24 h – 4 weeks after administration), the α-track frequency remained elevated. Conclusion The γ-H2AX+53BP1 assay is a potent method for detection of α-particle-induced DNA damages during treatment with or after accidental incorporation of radionuclides even at low absorbed doses. It may serve as a biomarker discriminating α- from β-emitters based on damage geometry.

DNA damage in peripheral blood mononuclear cells of patients undergoing anti-tuberculosis treatment

2012 ◽  
Vol 747 (1) ◽  
pp. 82-85 ◽  
Author(s):  
Larissa Ragozo Cardoso de Oliveira ◽  
Eliana Peresi ◽  
Francilene Capel Tavares ◽  
Camila Renata Corrêa ◽  
Damiana Tortolero Pierine ◽  
...  
Keyword(s):  
Dna Damage ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Tuberculosis Treatment ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

scholarly journals Interaction of Deubiquitinase 2A-DUB/MYSM1 with DNA Repair and Replication Factors

2020 ◽  
Vol 21 (11) ◽  
pp. 3762
Author(s):  
Carsten Kroeger ◽  
Reinhild Roesler ◽  
Sebastian Wiese ◽  
Adelheid Hainzl ◽  
Martina Vanessa Gatzka
Keyword(s):  
Mass Spectrometry ◽  
Dna Damage ◽  
Dna Repair ◽  
Transcriptional Activation ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Human Peripheral Blood ◽  
Cell Cycle Control ◽  
Mass Spectrometry Data ◽  
Peripheral Blood Mononuclear

The deubiquitination of histone H2A on lysine 119 by 2A-DUB/MYSM1, BAP1, USP16, and other enzymes is required for key cellular processes, including transcriptional activation, apoptosis, and cell cycle control, during normal hematopoiesis and tissue development, and in tumor cells. Based on our finding that MYSM1 colocalizes with γH2AX foci in human peripheral blood mononuclear cells, leukemia cells, and melanoma cells upon induction of DNA double-strand breaks with topoisomerase inhibitor etoposide, we applied a mass spectrometry-based proteomics approach to identify novel 2A-DUB/MYSM1 interaction partners in DNA-damage responses. Differential display of MYSM1 binding proteins significantly enriched after exposure of 293T cells to etoposide revealed an interacting network of proteins involved in DNA damage and replication, including factors associated with poor melanoma outcome. In the context of increased DNA-damage in a variety of cell types in Mysm1-deficient mice, in bone marrow cells upon aging and in UV-exposed Mysm1-deficient skin, our current mass spectrometry data provide additional evidence for an interaction between MYSM1 and key DNA replication and repair factors, and indicate a potential function of 2A-DUB/MYSM1 in DNA repair processes.

scholarly journals Kaempferol derivatives isolated from Lens culinaris Medik. reduce DNA damage induced by etoposide in peripheral blood mononuclear cells

2019 ◽  
Vol 8 (6) ◽  
pp. 896-907 ◽  
Author(s):  
Magdalena Kluska ◽  
Michał Juszczak ◽  
Daniel Wysokiński ◽  
Jerzy Żuchowski ◽  
Anna Stochmal ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Viability ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Lens Culinaris ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Aerial Parts ◽  
Kaempferol Glycoside ◽  
Blood Mononuclear Cells

Abstract Bioactive compounds isolated from plants are considered to be attractive candidates for cancer therapy. In this study, we examined the effect of kaempferol, its derivatives, the polyphenol fraction (PF) and an extract (EX) isolated from the aerial parts of Lens culinaris Medik. on DNA damage induced by etoposide in human cells. We also studied the effect of these compounds and their combinations on cell viability. The studies were conducted on HL-60 cells and human peripheral blood mononuclear cells (PBMCs). We used the comet assay in the alkaline version to evaluate DNA damage. To examine cell viability we applied the trypan blue exclusion assay. We demonstrated that kaempferol glycoside derivatives isolated from the aerial parts of Lens culinaris Medik. reduce DNA damage induced by etoposide in PBMCs, but do not have an impact on DNA damage in HL-60 cells. We also showed that kaempferol induces DNA damage in HL-60 cells and leads to an increase of DNA damage provoked by etoposide. Our data suggest that kaempferol derivatives can be further explored as a potential agent protecting normal cells against DNA damage induced by etoposide. Moreover, kaempferol's ability to induce DNA damage in cancer cells and to increase DNA damage caused by etoposide may be useful in designing and improving anticancer therapies.

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