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Ionizing radiation response of primary normal human lens epithelial cells
- Source :
- PLoS ONE, PLoS ONE, Vol 12, Iss 7, p e0181530 (2017)
- Publication Year :
- 2017
- Publisher :
- Public Library of Science (PLoS), 2017.
-
Abstract
- Whilst the cataractogenic potential of ionizing radiation has been known for over the past 120 years, little is known about radiation responses of lens cells. Our previous work was the first to evaluate the radiosensitivity of lens cells with the clonogenic assay, documenting that the survival of HLEC1 human lens epithelial cells is comparable to that of WI-38 human lung fibroblasts. Moreover, HLEC1 cells were found to contain subsets where irradiation stimulates proliferation or facilitates formation of abortive colonies with fewer cells than human fibroblasts. This study aims to gain insights into these mechanisms. Irradiation of HLEC1 cells with 10% survival dose caused a growth delay but did not reduce viability. HLEC1 cells at high cumulative population doubling level were more susceptible to radiogenic premature senescence than WI-38 cells. Concerning p53 binding protein 1 (53BP1) foci, HLEC1 cells harbored less spontaneous foci but more radiogenic foci than in WI-38 cells, and the focus number returned to spontaneous levels within 48 h postirradiation both in HLEC1 and WI-38. The chemical inhibition of DNA repair kinases ataxia telangiectasia mutated, DNA-dependent protein kinase or both delayed and attenuated the appearance and disappearance of radiogenic 53BP1 foci, increased radiogenic premature senescence and enhanced clonogenic inactivation. The DNA microarray analysis suggested both radiogenic stimulation and inhibition of cell proliferation. Treatment with conditioned medium from irradiated cells did not change growth and the plating efficiency of nonirradiated cells. These results partially explain mechanisms of our previous observations, such that unrepaired or incompletely repaired DNA damage causes a growth delay in a subset of HLEC1 cells without changing viability through induction of premature senescence, thereby leading to clonogenic inactivation, but that growth is stimulated in another subset via as yet unidentified mechanisms, warranting further studies.
- Subjects :
- 0301 basic medicine
Plating efficiency
Microarrays
lcsh:Medicine
Gene Expression
Ataxia Telangiectasia Mutated Proteins
DNA-Activated Protein Kinase
Animal Cells
Radiation, Ionizing
Medicine and Health Sciences
Cluster Analysis
DNA Breaks, Double-Stranded
lcsh:Science
Telomerase
Lens (Anatomy)
Cells, Cultured
Cellular Senescence
Connective Tissue Cells
Oligonucleotide Array Sequence Analysis
Staining
Multidisciplinary
Chemistry
Physics
Cell Staining
Nuclear Proteins
Bioassays and Physiological Analysis
Cell Processes
Connective Tissue
Physical Sciences
Cellular Types
Anatomy
Tumor Suppressor p53-Binding Protein 1
Research Article
Cell Survival
DNA damage
DNA repair
Ocular Anatomy
Biophysics
Research and Analysis Methods
Cell Line
03 medical and health sciences
Ocular System
Dosimetry
Lens, Crystalline
Genetics
Humans
Radiosensitivity
Clonogenic assay
Cell Proliferation
Cataracts
Cell growth
Gene Expression Profiling
lcsh:R
HEK 293 cells
Biology and Life Sciences
Epithelial Cells
Cell Biology
Fibroblasts
Ophthalmology
Biological Tissue
Gene Ontology
HEK293 Cells
030104 developmental biology
Specimen Preparation and Treatment
Cell culture
Lens Disorders
Cancer research
lcsh:Q
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- PLOS ONE
- Accession number :
- edsair.doi.dedup.....09533ffeab4c002692b76343cdc6d478