Particle Irradiation Induces FGF2 Expression in Normal Human Lens Cells

Chang, Polly Y.; Bjornstad, Kathleen A.; Chang, Edmond Chin‐Ping; McNamara, Morgan P.; Barcellos‐Hoff, Mary Helen; Lin, Sylvia; Aragon, Geraldine; Polansky, Jon R.; Lui, Ge Ming; Blakely, Eleanor A.

doi:10.1667/0033-7587(2000)154[0477:piifei]2.0.co;2

Cited by 25 publications

(11 citation statements)

References 45 publications

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“…This was unexpected as 0.5 Gy is a dose that inactivates clonogenic potential of 31% of clonogenic HLEC1 [11], although expression changes at later time points need to be tested. The time and dose point of 3 h after 4 Gy was based on reports by Chang et al who used pathway arrays and showed upregulation of FGF2 and CDKN1A and downregulation of cyclin G1, CDC2, CHK2, TIMP1, MMP-2, -3 and -9 at 3 h after irradiation of human LECs with 4 Gy of X-rays, protons, helium or iron ions [42–44]. Of these, upregulation of only FGF2 was observed in HLEC1 at p <0.05 and FDR <0.1, although upregulation of CDKN1B (p27 Kip1 ), downregulation of CCNA2 (cyclin A2) and CCNB1 (cyclin B1) were observed instead (S3 and S4 Tables).…”

Section: Discussionmentioning

confidence: 99%

Ionizing radiation response of primary normal human lens epithelial cells

Hamada

2017

PLoS ONE

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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.

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Section: Discussionmentioning

confidence: 99%

Ionizing radiation response of primary normal human lens epithelial cells

Hamada

2017

PLoS ONE

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“…28,36 In vivo, FGF2 released into the coronary circulation after vascular injury promotes human vascular smooth muscle cell proliferation. 4 Similar to mechanical damage, cell membrane injury from ionizing radiation induces FGF2 expression and release in endothelial and epithelial cells in vitro 5,23,24 and in vivo. 41 FGF2 enhances endothelial, epithelial, and hematopoetic cell survival after ionizing radiation, 18,19,22,23 and FGF2 release is critical to radiation damage repair.…”

Section: Discussionmentioning

confidence: 99%

Endothelial Cell Proliferation is Enhanced by Low Dose Non-Thermal Plasma Through Fibroblast Growth Factor-2 Release

et al. 2009

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Non-thermal dielectric barrier discharge plasma is being developed for a wide range of medical applications, including wound healing, blood coagulation, and malignant cell apoptosis. However, the effect of non-thermal plasma on the vasculature is unclear. Blood vessels are affected during plasma treatment of many tissues and may be an important potential target for clinical plasma therapy. Porcine aortic endothelial cells were treated in vitro with a custom non-thermal plasma device. Low dose plasma (up to 30 s or 4 J cm(-2)) was relatively non-toxic to endothelial cells while treatment at longer exposures (60 s and higher or 8 J cm(-2)) led to cell death. Endothelial cells treated with plasma for 30 s demonstrated twice as much proliferation as untreated cells five days after plasma treatment. Endothelial cell release of fibroblast growth factor-2 (FGF2) peaked 3 h after plasma treatment. The plasma proliferative effect was abrogated by an FGF2 neutralizing antibody, and FGF2 release was blocked by reactive oxygen species scavengers. These data suggest that low dose non-thermal plasma enhances endothelial cell proliferation due to reactive oxygen species mediated FGF2 release. Plasma may be a novel therapy for dose-dependent promotion or inhibition of endothelial cell mediated angiogenesis.

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“…LBNL investigated a role for radiation-induced changes in the expression of basic Fibroblast Growth Factor ( FGF-2 ) gene expression as part of the mechanism(s) underlying lens cell injury associated with cataract (Chang et al 2000). HLE cells were exposed to a single dose of protons (LET = 1.18 keV μm −1 ) or helium ions (LET = 7.2 keV μm −1 ) at the 88-inch cyclotron at LBNL.…”

Section: In Vitro Molecular Responses Of Hle During Post-exposure Latmentioning

confidence: 99%

Lauriston S. Taylor Lecture on Radiation Protection and Measurements

Blakely¹

2012

Health Physics

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The scientific basis for the physical and biological effectiveness of particle radiations has emerged from many decades of meticulous basic research. A diverse array of biologically relevant consequences at the molecular, cellular, tissue, and organism level have been reported, but what are the key processes and mechanisms that make particle radiation so effective, and what competing processes define dose dependences? Recent studies have shown that individual genotypes control radiation-regulated genes and pathways in response to radiations of varying ionization density. The fact that densely ionizing radiations can affect different gene families than sparsely ionizing radiations, and that the effects are dose- and time-dependent has opened up new areas of future research. The complex microenvironment of the stroma, and the significant contributions of the immune response have added to our understanding of tissue-specific differences across the linear energy transfer (LET) spectrum. The importance of targeted vs. nontargeted effects remain a thorny, but elusive and important contributor to chronic low dose radiation effects of variable LET that still needs further research. The induction of cancer is also LET-dependent, suggesting different mechanisms of action across the gradient of ionization density. The focus of this 35th Lauriston S. Taylor Lecture is to chronicle the step-by-step acquisition of experimental clues that have refined our understanding of what makes particle radiation so effective, with emphasis on the example of radiation effects on the crystalline lens of the human eye.

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Particle Irradiation Induces FGF2 Expression in Normal Human Lens Cells

Cited by 25 publications

References 45 publications

Ionizing radiation response of primary normal human lens epithelial cells

Ionizing radiation response of primary normal human lens epithelial cells

Endothelial Cell Proliferation is Enhanced by Low Dose Non-Thermal Plasma Through Fibroblast Growth Factor-2 Release

Lauriston S. Taylor Lecture on Radiation Protection and Measurements

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