Cataractogenesis following high-LET radiation exposure

Hamada, Nobuyuki; Sato, Tatsuhiko

doi:10.1016/j.mrrev.2016.08.005

Cited by 43 publications

(21 citation statements)

References 123 publications

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“…In its latest 2007 basic recommendations, the International Commission on Radiological Protection (ICRP) writes that gonads, bone marrow and the crystalline lens of the eye are among the most radiosensitive tissues in the body [3]. ICRP has classified radiation cataracts as tissue reactions (formerly called nonstochastic or deterministic effects) with a dose threshold below which no effect would occur, and has recommended an equivalent dose limit for the ocular lens of workers and public to prevent radiation cataracts [4,5]. Consideration of recent epidemiological evidence led ICRP to recommend in 2011 a threshold of 0.5 Gy (independent of rate of dose delivery and assuming progression of detectable opacities into vision-impairing cataracts) and an occupational equivalent dose limit for the lens of 20 mSv/year, averaged over defined periods of 5 years, with no single year exceeding 50 mSv): these are significant reductions from previously recommendations (i.e., a threshold for detectable opacities of 0.5–2 Gy for acute exposure and 5 Gy for highly fractionated or protracted exposures, a threshold for vision-impairing cataracts of 2–10 Gy for acute exposure and >8 Gy for highly fractionated or protracted exposures, and an occupational equivalent dose limit for the lens of 150 mSv/year) [6,7].…”

Section: Introductionmentioning

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: Introductionmentioning

confidence: 99%

Ionizing radiation response of primary normal human lens epithelial cells

Hamada

2017

PLoS ONE

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“…Hladik and Tapio review the epidemiology and biology of brain effects [3]. Shore provides an overview of cataract epidemiology [4], whereas Ainsbury et al reviews the biology of cataractogenesis following low linear energy transfer (LET) radiation exposures [5]; Hamada and Sato also review high-LET radiation cataractogenesis [6]. Grubber and Dörr consider the radiobiology of the oral mucosa, which is important in light of the adverse reactions to radiotherapy [7].…”

Section: Introductionmentioning

confidence: 99%

Special issue: Tissue reactions to ionizing radiation exposure

Hamada

Bouffler

Woloschak

2016

Mutation Research/Reviews in Mutation Research

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“…whereas nuclear cataracts are considered non-radiogenic. These data suggested a threshold for radiation-induced cataractogenesis of 0. are needed [190], and there is a discussion whether cataractogenesis should be considered as a deterministic or stochastic phenomenon [187,191,192]. In fact, peripheral lens epithelial cells repair DSBs after 20 and 100 mGy more slowly than peripheral circulating blood lymphocytes [181].…”

Section: Lens Opacities Among Interventional Cardiologistsmentioning

confidence: 99%

Progress in low dose health risk research

Averbeck

Salomaa

Bouffler

et al. 2018

Mutation Research/Reviews in Mutation Research

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People are more often exposed to low as opposed to high doses of ionising radiation (IR). Knowledge on the health risks associated with exposures to ionising radiation above 100 mGy is quite well established, while lower dose risks are inferred from higher level exposure information (ICRP). The health risk assessments are mainly based on epidemiological data derived from the atomic bombing of Hiroshima and Nagasaki, medical exposure studies and follow-up studies after nuclear accidents. For the estimation of long-term stochastic radiation health effects (such as cancer) and radiation protection purposes, a linear non-threshold (LNT) model is applied. However, the general validity of the LNT hypothesis for extrapolations from effects of high to low doses (<100 mGy) and low dose-rates (<6 mGy/h) has been questioned as epidemiological studies are statistically limited at low doses and unable to evaluate low dose and low dose-rate health risks (UNSCEAR). Thus, uncertainties on health risks need to be clarified with the help of mechanistic studies. The European Network of Excellence DoReMi (2010-2016) was designed to address some of the existing uncertainties and to identify research lines that are likely to be most informative for low dose risk assessment. The present review reports the results obtained from studies addressing the induction of cancer and non-cancer effects by low dose IR as well as on individual radiation sensitivity. It is shown that low dose and low dose-rate effects are the result of complex network responses including genetic, epigenetic, metabolic and immunological regulation. Evidence is provided for the existence of nonlinear biological responses in the low and medium dose range as well as effects other than the classical DNA damage. Such effects may have a bearing on the quantitative and qualitative judgements on health effects induced by low dose radiations.

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Cataractogenesis following high-LET radiation exposure

Cited by 43 publications

References 123 publications

Ionizing radiation response of primary normal human lens epithelial cells

Ionizing radiation response of primary normal human lens epithelial cells

Special issue: Tissue reactions to ionizing radiation exposure

Progress in low dose health risk research

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