Ionizing radiation‐induced death in bovine lens epithelial cells: Mechanisms and influence of irradiation dose rate

Belkacémi, Yazid; Piel, Gaëlle; Rat, Patrice; Julia, Fredéric; Touboul, E.; Housset, M.; Warnet, Jean‐Michel

doi:10.1002/1097-0215(20000620)90:3<138::aid-ijc3>3.3.co;2-h

Cited by 4 publications

(8 citation statements)

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“…The cell survival curve was strongly exponential, without a shoulder in the low-dose range, and D37 values ranged between 2.08 and 3.28 Gy. In a dose-rate study [29], we observed a higher lethality following a single fraction of 10 Gy delivered at a dose rate of 2 Gy/min. In a study of the anticataractogenic effects of a superoxide dis- mutase-like compound (Tempol ) in rabbits, Sasaki et al [14] used the same dose and dose rate as in our current study.…”

Section: Discussionmentioning

confidence: 79%

“…Their methods, comprised of extracting lens from irradiated animals or exposing lenses directly to toxic substances, does not accurately evaluate cell mortality nor their antioxidant capacities. To avoid this bias and to study labile markers such as intracellular GSH, we used a series of validated fluorimetric assays performed directly on live bovine cells [29,35,36].…”

Section: Discussionmentioning

confidence: 99%

“…The details of cell preparation have been described elsewhere [29]. In summary, growing cells were obtained from primary cultures.…”

Section: Cell Preparationmentioning

confidence: 99%

“…The details of the high dose-rate irradiation technique have been described elsewhere [29]. A single dose of 10 Gy was delivered using a 4-MV linear accelerator with a dose rate of 2 Gy/min.…”

Section: Irradiation Technique and Cell Culture After Irradiationmentioning

confidence: 99%

“…Each Petri dish was scanned to quantify the UV-HO fluorescent signal from intracellular DNA. The methodology has been described elsewhere [29,35,36,38].…”

Section: Evaluation Of Chromatin Condensation With Fluorimetric Hoechmentioning

confidence: 99%

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Lens epithelial cell protection by aminothiol WR-1065 and anetholedithiolethione from ionizing radiation

Belkacémi¹,

Rat²,

Piel³

et al. 2001

Int. J. Cancer

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SUMMARY Lens epithelium disorganization, glutathione (GSH) depletion, and epithelial cell death have been incriminated in the cytopathogenic mechanisms that lead to cataract formation following UVB and x-ray exposures. The objective of this study was to determine the in vitro capacity of the aminothiol WR-1065, the active metabolite of amifostine, and anetholedithiolethione (ADT or Sulfarlem ) to protect bovine lens epithelial cells against x-ray irradiation. WR-1065 and ADT were used at a concentration of 20 M. A single dose of 10 Gy was delivered at a rate of 2 Gy/min. Fluorimetric assays were then performed using a neutral red probe to evaluate cell viability, a Hoechst 33342 probe (HO) to evaluate nuclear condensation and apoptosis, and a monobromobimane probe to estimate the intracellular GSH pool. Twenty-four hours after x-ray exposure, cells pretreated with WR-1065 showed increased GSH levels, improved cell viability, and decreased HO fluorescence in addition to a lesser proportion of cells with apoptotic nuclear modifications. Between 72 and 120 hr postirradiation, ADT-pretreated cells also showed increased intracellular GSH levels and cell viability and decreased HO fluorescence and apoptotic cell morphology. This in vitro study demonstrates that WR-1065 and ADT protects lens epithelial cells from x-ray injury; thus, ADT and amifostine are appropriate candidates for clinical trials in humans. They are currently used in preventing radiation-induced xerostomia and should be further tested in the prevention of late radiation-induced ocular complications such as sicca syndrome and cataract.

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 99%

“…The details of cell preparation have been described elsewhere [29]. In summary, growing cells were obtained from primary cultures.…”

Section: Cell Preparationmentioning

confidence: 99%

Section: Irradiation Technique and Cell Culture After Irradiationmentioning

confidence: 99%

“…Each Petri dish was scanned to quantify the UV-HO fluorescent signal from intracellular DNA. The methodology has been described elsewhere [29,35,36,38].…”

Section: Evaluation Of Chromatin Condensation With Fluorimetric Hoechmentioning

confidence: 99%

See 3 more Smart Citations

Lens epithelial cell protection by aminothiol WR-1065 and anetholedithiolethione from ionizing radiation

Belkacémi¹,

Rat²,

Piel³

et al. 2001

Int. J. Cancer

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ICRP PUBLICATION 118: ICRP Statement on Tissue Reactions and Early and Late Effects of Radiation in Normal Tissues and Organs — Threshold Doses for Tissue Reactions in a Radiation Protection Context

Stewart¹,

Akleyev²,

et al. 2012

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This report provides a review of early and late effects of radiation in normal tissues and organs with respect to radiation protection. It was instigated following a recommendation in Publication 103 (ICRP, 2007), and it provides updated estimates of 'practical' threshold doses for tissue injury defined at the level of 1% incidence. Estimates are given for morbidity and mortality endpoints in all organ systems following acute, fractionated, or chronic exposure. The organ systems comprise the haematopoietic, immune, reproductive, circulatory, respiratory, musculoskeletal, endocrine, and nervous systems; the digestive and urinary tracts; the skin; and the eye. Particular attention is paid to circulatory disease and cataracts because of recent evidence of higher incidences of injury than expected after lower doses; hence, threshold doses appear to be lower than previously considered. This is largely because of the increasing incidences with increasing times after exposure. In the context of protection, it is the threshold doses for very long follow-up times that are the most relevant for workers and the public; for example, the atomic bomb survivors with 40-50years of follow-up. Radiotherapy data generally apply for shorter follow-up times because of competing causes of death in cancer patients, and hence the risks of radiation-induced circulatory disease at those earlier times are lower. A variety of biological response modifiers have been used to help reduce late reactions in many tissues. These include antioxidants, radical scavengers, inhibitors of apoptosis, anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, growth factors, and cytokines. In many cases, these give dose modification factors of 1.1-1.2, and in a few cases 1.5-2, indicating the potential for increasing threshold doses in known exposure cases. In contrast, there are agents that enhance radiation responses, notably other cytotoxic agents such as antimetabolites, alkylating agents, anti-angiogenic drugs, and antibiotics, as well as genetic and comorbidity factors. Most tissues show a sparing effect of dose fractionation, so that total doses for a given endpoint are higher if the dose is fractionated rather than when given as a single dose. However, for reactions manifesting very late after low total doses, particularly for cataracts and circulatory disease, it appears that the rate of dose delivery does not modify the low incidence. This implies that the injury in these cases and at these low dose levels is caused by single-hit irreparable-type events. For these two tissues, a threshold dose of 0.5Gy is proposed herein for practical purposes, irrespective of the rate of dose delivery, and future studies may elucidate this judgement further.

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Heavy Metal Pad Shielding during Fluoroscopic Interventions

Dromi

Wood

Oberoi

et al. 2006

Journal of Vascular and Interventional Radiology

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Significant direct and scatter radiation doses to patient and physician may result from routine interventional radiology practice. A lead-free disposable tungsten antimony shielding pad was tested in phantom patients during simulated diagnostic angiography procedures. Although the exact risk of low doses of ionizing radiation is unknown, dramatic dose reductions can be seen with routine use of this simple, sterile pad made from lightweighttungsten antimony material.THE increasing use of imaging to guide procedures has been accompanied by public health concerns about radiation exposure to patients and health care personnel (1). Whenever a medical image is obtained, a compromise must be made between the quality of the image and the radiation dose used to make that image. Certainly, the lowest dose that can produce a diagnostic image is ideal, which leads to the ALARA principle ("As Low As Reasonably Achievable") (2). This concept is paramount with the use of fluoroscopy because of continuous x-ray production and real-time imaging.Interventional radiology procedures may expose the patient and physician to the effects of direct and scatter radiation (3). Patient exposure is usually mostly direct radiation,whereas physician exposure may be mostly scatter radiation (4). Biologic effects of ionizing radiation can be categorized as acute or delayed. Although the acute effects of radiation are not commonly a problem, the delayed effects remain a poorly quantifiable concern. Because the delayed effects may take years or decades to appear, they are difficult to distinguish from effects caused by other sources. For this reason, they are considered stochastic rather than deterministic effects. The likelihood of a stochasticeffect is directly related to the radiation dose, but its severity is not related to the total dose received. Examples of stochastic effects include carcinogenesis and genetic mutation. This type of effect is of particular concern because it may occur at any dose and there is no threshold dose at which it occurs. However, the lower the dose received, the lower the incidence of consequences that will develop. The principle of ALARA is based on this concept. The deterministic effects do have a threshold dose, and beyond this threshold, the severity is directly related to the dose (ie, cataracts, skin burns) (5,6).In fluoroscopy, the exposure to ionizing radiation can be diminished in several ways, including judicious use of fluoroscopy, use of intermittent or pulsed fluoroscopy, holding of the last image, reduction of field size (ie, collimation), and minimization of fieldoverlap (3). The use of intermittent fluoroscopy can diminish the radiation by 20%-70% (7). Additional methods described include minimization of the distance between the patient and the intensifier, maximization of the distance between the patient and the operator, choice of appropriate parameters to operate the machine, and use of movable lead surface shields (8,9) and shielded gloves (10,11 NIH-PA Author ManuscriptNIH-PA Author M...

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Ionizing radiation‐induced death in bovine lens epithelial cells: Mechanisms and influence of irradiation dose rate

Cited by 4 publications

References 1 publication

Lens epithelial cell protection by aminothiol WR-1065 and anetholedithiolethione from ionizing radiation

Lens epithelial cell protection by aminothiol WR-1065 and anetholedithiolethione from ionizing radiation

ICRP PUBLICATION 118: ICRP Statement on Tissue Reactions and Early and Late Effects of Radiation in Normal Tissues and Organs — Threshold Doses for Tissue Reactions in a Radiation Protection Context

Heavy Metal Pad Shielding during Fluoroscopic Interventions

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