ArticleCell death discovery2016
Induction and inhibition of the pan-nuclear gamma-H2AX response in resting human peripheral blood lymphocytes after X-ray irradiation.
Article in Cell death discovery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 54 citations in OpenAlex.
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- Dynamic γ-H2AX response in blood lymphocytes for prediction of radiotherapy induced bladder toxicity in cervical cancer patients.The Indian journal of medical research · 2026Article
- Androgen receptor contributes to radioresistance through DNA repair and autophagy in AR-positive prostate cancer cells.bioRxiv : the preprint server for biology · 2025Article
- Temporal and spatial pattern of DNA damage in neurons following spinal cord Injury in mice.Journal of biomedical science · 2025Article
- Relevance of Immunohistochemistry for Tumorigenic Tumor-Infiltrating Neutrophils and Reverse Polarity in Colonic Micropapillary Adenocarcinoma: A Case Report.Case reports in pathology · 2025Article
- PARG-deficient tumor cells have an increased dependence on EXO1/FEN1-mediated DNA repair.The EMBO journal · 2024Article
- Particulate matter composition drives differential molecular and morphological responses in lung epithelial cells.PNAS nexus · 2024Article
- The Ultraviolet Irradiation of Keratinocytes Induces Ectopic Expression of LINE-1 Retrotransposon Machinery and Leads to Cellular Senescence.Biomedicines · 2023Article
- High-throughput measurement of double strand break global repair phenotype in peripheral blood mononuclear cells after long-term cryopreservation.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2023Article
- High-Throughput γ-H2AX Assay Using Imaging Flow Cytometry.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Short-term and bystander effects of radiation on murine submandibular glands.Disease models & mechanisms · 2022Article
- Tools used to assay genomic instability in cancers and cancer meiomitosis.Journal of cell communication and signaling · 2022Review
- Tightly Focused Femtosecond Laser Radiation Induces DNA Double-Strand Breaks in Human Tumor Cells.Bulletin of experimental biology and medicine · 2022Article
- Microfluidic chip-based long-term preservation and culture of engineering bacteria for DNA damage evaluation.Applied microbiology and biotechnology · 2022Article
- Cystatin B deficiency results in sustained histone H3 tail cleavage in postnatal mouse brain mediated by increased chromatin-associated cathepsin L activity.Frontiers in molecular neuroscience · 2022Article
- CHK1 protects oncogenic KRAS-expressing cells from DNA damage and is a target for pancreatic cancer treatment.Cell reports · 2021Article
- Immunocytochemical Localization of XRCC1 and γH2AX Foci Induced by Tightly Focused Femtosecond Laser Radiation in Cultured Human Cells.Molecules (Basel, Switzerland) · 2021Article
- Evaluation of Calyculin A Effect on γH2AX/53BP1 Focus Formation and Apoptosis in Human Umbilical Cord Blood Lymphocytes.International journal of molecular sciences · 2021Article
- Integrin-Linked-Kinase Overexpression Is Implicated in Mechanisms of Genomic Instability in Human Colorectal Cancer.Digestive diseases and sciences · 2021Article
- Detection and quantification of γ-H2AX using a dissociation enhanced lanthanide fluorescence immunoassay.Scientific reports · 2021Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human peripheral blood lymphocytes (HPBLs) are one of the most sensitive cells to ionizing radiation (IR) in the human body, and IR-induced DNA damage and functional impairment of HPBLs are the adverse consequences of IR accidents and major side effects of radiotherapy. Phosphorylated H2AX (γH2AX) is a sensitive marker for DNA double-strand breaks, but the role and regulation of the pan-nuclear γH2AX response in HPBLs after IR remain unclear. We herein demonstrated that the pan-nuclear γH2AX signals were increased in a time- and dose-dependent manner, colocalized with >94% of TUNEL apoptotic staining, and displayed a typical apoptotic pattern in resting HPBLs after low LET X-ray IR. In addition, the X-irradiation-induced pan-nuclear p-ATM and p-DNA-PKcs responses also occurred in resting HPBLs, and were colocalized with 92-95% of TUNEL staining and 97-98% of the pan-nuclear γH2AX signals, respectively, with a maximum at 6 h post irradiation, but disappeared at 24 h post irradiation. Moreover, ATM/DNA-PKcs inhibitor KU55933, p53 inhibitor PFT-μ and pan-caspase inhibitor ZVAD-fmk significantly decreased X-irradiation-induced pan-nuclear γH2AX signals and TUNEL staining, protected HPBLs from apoptosis, but decreased the proliferative response to mitogen in X-irradiated HPBLs. Notably, whereas both KU55933 and PFT-μ increased the IR-induced chromosome breaks and mis-repair events through inhibiting the formation of p-ATM, p-DNA-PKcs and γH2AX foci in X-irradiated HPBLs, the ZVAD-fmk did not increase the IR-induced chromosomal instability. Taken together, our data indicate that pan-nuclear γH2AX response represents an apoptotic signal that is triggered by the transient pan-nuclear ATM and DNA-PKcs activation, and mediated by p53 and pan-caspases in X-irradiated HPBLs, and that caspase inhibitors are better than ATM/DNA-PKcs inhibitors and p53 inhibitors to block pan-nuclear γH2AX response/apoptosis and protect HPBLs from IR.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.