Low dose, low-LET ionizing radiation-induced radioadaptation and associated early responses in unirradiated cells

Iyer, Rashi; Lehnert, Bruce E.

doi:10.1016/s0027-5107(02)00068-4

Cited by 166 publications

(102 citation statements)

References 34 publications

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“…Radiation-induced adaptive responses are commonly reported in the literature (1, 2). However, there are few reports of an ICCMinduced adaptive response against a direct dose ( [23][24][25]. The magnitude of the observed ''ICCM adaptive response'' was 10-15% sparing of cell survival.…”

Section: Discussionmentioning

confidence: 99%

“…Data from our laboratory have shown that bystander-induced cell death can be blocked in HPV-G cells incubated in ICCM containing NAC (35). Iyer and Lehnert (25) suggest that bystander-induced adaptive responses could be due to increased levels of AP DNA endonucleases (APE), induced as a result of an increase in sublethal levels of ROS. Lyng et al (18) reported an increase in ROS after exposure of HPV-G cells to ICCM.…”

Section: Discussionmentioning

confidence: 99%

“…This study also reported that treatment with medium from cells exposed to 2 cGy X rays can induce a ''bystander adaptive response'' in C3H 10T1/2 cells against a higher dose of direct radiation (4 Gy X rays). Iyer and Lehnert (25) reported that when normal human lung fibroblasts (HFL-1) were irradiated with 1 cGy of ␥ rays and the supernatants were transferred to unirradiated HFL-1 cells, a bystander adaptive response was observed against 2 or 4 Gy of X rays. This shows that medium from irradiated cells, which contains the currently unknown cytotoxic bystander factor(s), can induce an adaptive response against a subsequent direct dose.…”

Section: Galley 106mentioning

confidence: 99%

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Modulation of Radiation Responses by Pre-exposure to Irradiated Cell Conditioned Medium

et al. 2007

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CitationModulation of radiation responses by pre-exposure to irradiated cell conditioned medium. The aim of this study was to investigate whether exposure of HPV-G cells to irradiated cell conditioned medium (ICCM) could induce an adaptive response if the cells were subsequently challenged with a higher ICCM dose. Clonogenic survival and major steps in the cascade leading to apoptosis, such as calcium influx and loss of mitochondrial membrane potential, were examined to determine whether these events could be modified by giving a priming dose of ICCM before the challenge dose. Clonogenic survival data indicated an ICCMinduced adaptive response in HPV-G cells ''primed'' with 5 mGy or 0.5 Gy ICCM for 24 h and then exposed to 0.5 Gy or 5 Gy ICCM. Reactive oxygen species (ROS) were found to be involved in the bystander-induced cell death. Calcium fluxes varied in magnitude across the exposed cell population, and a significant number of the primed HPV-G cells did not respond to the challenge ICCM dose. No significant loss of mitochondrial membrane potential was observed when HPV-G cells were exposed to 0.5 Gy ICCM for 24 h followed by exposure to 5 Gy ICCM for 6 h. Exposure of HPV-G cells to 5 mGy ICCM for 24 h followed by exposure to 0.5 Gy ICCM for 18 h caused a significant increase in mitochondrial mass and a change in mitochondrial location, events associated with the perpetuation of genomic instability. This study has shown that a priming dose of ICCM has the ability to induce an adaptive response in HPV-G cells subsequently exposed to a challenge dose of ICCM. ᭧

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Galley 106mentioning

confidence: 99%

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Modulation of Radiation Responses by Pre-exposure to Irradiated Cell Conditioned Medium

et al. 2007

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“…A clonogenic survival assay is an additional method that has been frequently used to characterize the IR-induced cytoprotective responses. In this case, the pre-irradiated cells were shown to withstand subsequent challenging doses of IR which would otherwise abolish their colony formation (Wolff, 1992;Iyer and Lehnert, 2002). This suggests that the pre-irradiation either enhanced cellular growth competence or reduced the challenge-induced cell death.…”

Section: Ionizing Radiation Induces Blockade Of C-jun N-terminal Kinamentioning

confidence: 95%

Ionizing radiation induces blockade of c-Jun N-terminal kinase-dependent cell death pathway in a manner correlated with p21Cip/WAF1 induction in primary cultured normal human fibroblasts

et al. 2005

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During radiotherapy of cancer, neighboring normal cells may receive sub-lethal doses of radiation. To investigate whether such low levels of radiation modulate normal cell responses to death stimuli, primary cultured human fibroblasts were exposed to various doses of γ-rays. Analysis of cell viability using an exclusion dye propidium iodide revealed that the irradiation up to 10 Gy killed the fibroblasts only to a minimal extent. In contrast, the cells efficiently lost their viability when exposed to 0.5-0.65 mM H2O2. This type of cell death was accompanied by JNK activation, and was reversed by the use of a JNK-specific inhibitor SP600125. Interestingly, H 2 O 2 failed to kill the fibroblasts when these cells were pre-irradiated, 24 h before H 2 O 2 treatment, with 0.25-0.5 Gy of γ-rays. These cytoprotective doses of γ-rays did not enhance cellular capacity to degrade H2O2, but elevated cellular levels of p21 Cip/WAF1 , a p53 target that can suppress H 2 O 2 -induced cell death by blocking JNK activation. Consistently, H 2 O 2 -induced JNK activation was dramatically suppressed in the pre-irradiated cells. The overall data suggests that ionizing radiation can impart normal fibroblasts with a survival advantage against oxidative stress by blocking the process leading to JNK activation.

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“…Since the original experiments reported in 1984 [5], numerous data have shown the existence of such a response with a variety of endpoints in various cell types [6]. Although bystander effect and adaptive response are important parameters for low-dose radiation response, there are only limited data available comparing the two effects [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

The Yin and Yang of Low-Dose Radiobiology

Hei¹,

Zhou²,

Ivanov³

Radiation Health Risk Sciences

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Summary. Two confl icting phenomena, bystander effect and adaptive response, are important in determining the biological responses at low doses of radiation and have the potential to impact the shape of the dose-response relationship. Using the Columbia University charged-particle microbeam and the highly sensitive humanhamster hybrid (A L ) cells mutagenic assay, we show here that nonirradiated cells acquire mutagenesis through direct contact with cells whose nuclei have been traversed with a lethal dose of 20 alpha (α-)particles each. Pretreatment of cells with a low dose of X-rays 4 h before α-particle irradiation signifi cantly decreased this bystander mutagenic response. Although adaptive response is largely protective in nature and the bystander response, in general, signifi es detrimental effects, the two processes share many common characteristics. There is evidence that extracellular signal-related kinase (ERK), nuclear factor-κB, cytokines, and mitochondrial functions play an important role in the bystander effects. However, all these signaling events are applicable to the adaptive response as well. These data suggest a common lineage between these two stress-related phenomena. A better understanding of how these two effects interact at the cellular, tissue, and organ levels will address some of the pressing issues on target size, radiation dose response, and, ultimately, low dose risk assessment.

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Low dose, low-LET ionizing radiation-induced radioadaptation and associated early responses in unirradiated cells

Cited by 166 publications

References 34 publications

Modulation of Radiation Responses by Pre-exposure to Irradiated Cell Conditioned Medium

Modulation of Radiation Responses by Pre-exposure to Irradiated Cell Conditioned Medium

Ionizing radiation induces blockade of c-Jun N-terminal kinase-dependent cell death pathway in a manner correlated with p21Cip/WAF1 induction in primary cultured normal human fibroblasts

The Yin and Yang of Low-Dose Radiobiology

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