Determining if low dose hyper-radiosensitivity (HRS) can be exploited to provide a therapeutic advantage: A cell line study in four glioblastoma multiforme (GBM) cell lines

Schoenherr, D.; Krueger, S.A.; Martin, Lynn; Marignol, Laure; Wilson, George; Marples, Brian

doi:10.3109/09553002.2013.825061

Cited by 27 publications

(27 citation statements)

References 37 publications

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“…Accumulating evidence suggests that it may have varied implications on radiotherapy practices. 130,131 While in vivo studies continue to provide insights into the potentially clinical implications of HRS/IRR in terms of exploitation of the response for a therapeutic benefit and implications for normal tissue reactions, no changes in current practices can be made until the underlying mechanism is fully understood. However, this would not be extensively discussed in here since the dose level is relatively higher than the dose levels ( 0.1 Gy or occupationally 0.2 Gy low LET radiation) effectively inducing hormesis and AR.…”

Section: The Elusively Multiple Mechanisms Underlying the Effects Of mentioning

confidence: 99%

Low‐dose radiation may be a novel approach to enhance the effectiveness of cancer therapeutics

Yang

Jiang

et al. 2016

Intl Journal of Cancer

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It has been generally accepted that both natural and man-made sources of ionizing radiation contribute to human exposure and consequently pose a possible risk to human health. However, accumulating evidence has shown that the biological effects of low-dose radiation (LDR) are different from those of high-dose radiation. LDR can stimulate proliferation of normal cells and activate their defense systems, while these biological effects are not observed in some cancer cell types. Although there is still no concordance on this matter, the fact that LDR has the potential to enhance the effects of cancer therapeutics and reduce the toxic side effects of anti-cancer therapy has garnered significant interest. Here, we provide an overview of the current knowledge regarding the experimental data detailing the different responses of normal and cancer tissues to LDR, the underlying mechanisms, and its significance in clinical application.

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Section: The Elusively Multiple Mechanisms Underlying the Effects Of mentioning

confidence: 99%

Low‐dose radiation may be a novel approach to enhance the effectiveness of cancer therapeutics

Yang

Jiang

et al. 2016

Intl Journal of Cancer

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“…However, some studies have reported that LDFRT at intervals of several hours does not enhance the cytotoxic effect [ 15 – 17 ]. On the other hand, other studies have reported that LDFRT at short time intervals (2 or 3 min) shows enhanced cytotoxic effects [ 18 – 20 ]. Depending on the unit dose and the total dose, LDFRT alone takes at least 15 min or more, even when short, 3-min intervals are used.…”

Section: Introductionmentioning

confidence: 98%

Impact of time interval and dose rate on cell survival following low-dose fractionated exposures

Terashima

Hosokawa

Tsuruga

et al. 2017

Journal of Radiation Research

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Enhanced cell lethality, also known as hyper-radiosensitivity, has been reported at low doses of radiation (≤0.5 Gy) in various cell lines, and is expected to be an effective cancer therapy. We conducted this study to examine the impact of time interval and dose rate of low-dose fractionated exposures with a short time interval. We evaluated the cell-survival rates of V79 and A549 cells using clonogenic assays. We performed fractionated exposures in unit doses of 0.25, 0.5, 1.0 and 2.0 Gy. We exposed the cells to 2 Gy of X-rays (i) at dose-rates of 1.0, 1.5 and 2.0 Gy/min at 1-min intervals and (ii) at a dose-rate of 2.0 Gy/min at 10-s, 1-min and 3-min intervals by fractionated exposures. Apoptosis and cell cycle analyses were also evaluated in the fractionated exposures (unit dose 0.25 Gy) and compared with single exposures by using flow cytometry. Both cell-type survival rates with fractionated exposures (unit dose 0.25 Gy) with short time intervals were markedly lower than those for single exposures delivering the same dose. When the dose rates were lower, the cytotoxic effect decreased compared with exposure to a dose-rate of 2.0 Gy/min. On the other hand, levels of apoptosis and cell cycle distribution were not significantly different between low-dose fractionated exposures and single exposures in either cell line. These results indicate that a stronger cytotoxic effect was induced with low-dose fractionated exposures with a short time interval for a given dose due to the hyper-radiosensitivity phenomenon, suggesting that dose rates are important for effective low-dose fractionated exposures.

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“…. (28) Notice that the difference between this matrix and the one in the previous subsection in (18) is the nonzero parameter θ in (28). As a check, this derivation should result in that of the last subsection when θ = 0.…”

Section: Radiation Exposure Time Too Short For Cell Progression But Smentioning

confidence: 69%

Effects of G2 checkpoint dynamics on the low-dose hyper-radiosensitivity

Olobatuyi

Vries

Hillen

2017

Preprint

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We develop and analyze a system of differential equations to investigate the effects of G2 checkpoint dynamics on the low-dose hyper-radiosensitivity. In experimental studies, it has been found that certain cell lines are more sensitive to low-dose radiation than would be expected from the classical Linear Quadratic model (LQ model). In fact, it is frequently observed that cells incur more damage at a low dose (say 0.3 Gy) than at higher dose (say 1 Gy). This effect has been termed hyper-radiosensitivity (HRS). The HRS is followed by a period of relative radioresistance (per unit dose) of cell kill over the dose range of ∼ 0.5 − 1 Gy. This latter phenomenon is termed increased radioresistance (IRR). These effects depend on the type of cells and on their phase in the cell cycle. Here we focus on the HRS phenomenon by fitting a model for the cell cycle that includes G2-checkpoint dynamics and radiation treatment to surviving fraction data for different cell lines including glioma cells, prostate cancer cells, as well as to cell populations that are enriched in certain phases of the cell cycle. The HRS effect is measured in the literature through αs α , the ratio of slope α s of the surviving fraction curve at zero dose to slope α of the corresponding LQ model. We derive an explicit formula for this ratio and we show that it corresponds very closely to experimental observations. Finally, we can identify the dependence of this ratio on the surviving fraction at 2 Gy. It was speculated in the literature that such a relation exists. Our theoretical analysis will help to more systematically identify the HRS in cell lines and opens doors to analyze its use in cancer treatment.PACS and mathematical subject classification numbers as needed.

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Determining if low dose hyper-radiosensitivity (HRS) can be exploited to provide a therapeutic advantage: A cell line study in four glioblastoma multiforme (GBM) cell lines

Abstract: Ultra-fractionation (10 × 0.2 Gy) is an effective modality for killing glioma cell lines compared with standard 2 Gy dosing when multiple days of treatment are given.

Cited by 27 publications

References 37 publications

Low‐dose radiation may be a novel approach to enhance the effectiveness of cancer therapeutics

Low‐dose radiation may be a novel approach to enhance the effectiveness of cancer therapeutics

Impact of time interval and dose rate on cell survival following low-dose fractionated exposures

Effects of G2 checkpoint dynamics on the low-dose hyper-radiosensitivity

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