Pharmacological approach to increasing the retention of radiation-induced γ-H2AX foci using phosphatase inhibitors: significance in radiation biodosimetry.

J Radiol Prot

Department of Radiation Biology and Toxicology, School of Life Sciences, Manipal Academy of Higher Education, Manipal 576 104, Karnataka, India.

Published: February 2018


Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article Abstract

In a scenario of accidental mass radiation exposure transportation and analysis of samples may take some time, resulting in loss of biomarker information over this period. The present study aims to use phosphatase inhibitors for longer retention of focal signals to adopt γ-H2AX as a biodosimetric biomarker for the management of early triage. Peripheral blood lymphocytes isolated from healthy individuals were irradiated in vitro with x-rays and γ-H2AX foci were analysed using fluorescent microscopy and flow cytometric methods. Further, the effect of protein phosphatase 2A inhibitors such as calyculin A, fostriecin and okadiac acid on the retention of foci was studied. Fluorescent microscopy was found to be a more sensitive method than flow cytometry. Calyculin A showed significant retention of focal signals at 6 h with 1.5-fold increased retention compared to radiation alone; this may prove beneficial in early triage management because of a better dose approximation.

Download full-text PDF

Source
http://dx.doi.org/10.1088/1361-6498/aaa97aDOI Listing

Publication Analysis

Top Keywords

phosphatase inhibitors
12
γ-h2ax foci
8
retention focal
8
focal signals
8
early triage
8
fluorescent microscopy
8
retention
5
pharmacological approach
4
approach increasing
4
increasing retention
4

Similar Publications

Background: PPM1D (protein phosphatase Mg⁺/Mn⁺ dependent 1D) is a Ser/Thr phosphatase that negatively regulates p53 and functions as an oncogenic driver. Its gene amplification and overexpression are frequently observed in various malignancies and disruption of PPM1D degradation has also been reported as a cause of cancer progression. However, the precise mechanisms regulating PPM1D stability remain to be elucidated.

View Article and Find Full Text PDF

Chronic myeloid leukemia (CML), a myeloproliferative neoplasm, is characterized by the fusion gene, which results in constitutive tyrosine kinase activity. While tyrosine kinase inhibitors (TKIs) have significantly improved CML outcomes, resistance and the persistence of leukemic stem cells remain major clinical challenges. Curcumin, a natural polyphenol derived from , has demonstrated potential anticancer properties.

View Article and Find Full Text PDF

Selected comparative aspects and unexpected findings in acute phase proteins and other biomarkers of animal health and welfare.

Res Vet Sci

September 2025

Interdisciplinary Laboratory of Clinical Pathology, Interlab-UMU, Campus of Excellence Mare Nostrum, University of Murcia, 30100 Murcia, Spain. Electronic address:

Recent years have seen advances in clinical biochemistry of domestic animals which have highlighted comparative differences between species and have also identified fundamental aspects of the biochemical mechanisms in physiological conditions and disease, that have implications across species, including human, health and welfare. From investigations in diverse species using biochemical, immunological, proteomic and metabolomic approaches a series of species particularities and unexpected results for some biomarkers have been made. These observations cover (1) the differences between species in the acute phase protein (APP) response to infection and inflammation; (2) the non-hepatic synthesis and release in the mammary gland, adipose tissue and intestine of APP (3) the response of haptoglobin (HP) as a biomarker for stress; (4) observations in non-mammalian species related to hemopexin and HP; (5) the response of bile acids in milk to mastitis; (6) barley serine protease inhibitors being identified in bovine faeces; (7) alkaline phosphatase being present in bovine nasal secretion; (8) saliva findings with analytes such as adenine deaminase showing different activity between saliva and serum and a detergent-like surfactant protein, latherin being found in equine saliva and sweat and (9) serum enzymes and selective muscle protein reaction of Atlantic salmon as an example of the differences in biochemistry between terrestrial and aquatic species.

View Article and Find Full Text PDF

Chronic treatment with fluoxetine, a widely prescribed selective serotonin reuptake inhibitor (SSRI), is known to promote neural plasticity. The role of fluoxetine in plasticity has been particularly tied to parvalbumin-positive interneurons, a key population of GABAergic neurons that regulate inhibitory tone and network stability. While our previous studies have highlighted fluoxetine-induced plasticity in the visual cortex and hippocampus, its cell-type-specific effects in the prefrontal cortex (PFC) remain unclear.

View Article and Find Full Text PDF

A prolyl oligopeptidase ligand blocks memory deficit in a repeated mild traumatic brain injury model.

Exp Neurol

September 2025

Division of Pharmacology and Pharmacotherapy, Drug Research Programme, Faculty of Pharmacy, University of Helsinki, Finland; Department of Pharmacology, Faculty of Medicine, University of Helsinki, Finland. Electronic address:

Traumatic brain injury (TBI) impacts up to 60 million people annually. Both severe TBIs and repeated mild TBIs (rmTBIs) can lead to persistent symptoms such as cognitive deficits, and even neurodegenerative diseases like chronic traumatic encephalopathy (CTE). To date, no therapies exist to mitigate the risk of CTE or other chronic symptoms post-TBI.

View Article and Find Full Text PDF