Radiation-induced genomic instability and persisting oxidative stress in primary bone marrow cultures

Clutton, S.M.; Townsend, K. M. S.; Walker, Chandler L.; Ansell, Jake; Wright, Esmond

doi:10.1093/carcin/17.8.1633

Cited by 245 publications

(117 citation statements)

References 10 publications

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“…The data in Kadhim et al (1997) and suggest that genetic factors leading to expression of chromosomal instability may be counteracted by other factors, which cause a long-term programmed cell death response to radiation. The data in this paper, showing that ICCM is able, in the long-term, to induce ROS, which was shown by Clutton et al (1996) to lead to chromosomal instability, and also to initiate the apoptotic cascade, means that the signal produces a response in cells which can lead to death or to persistence of damage. The fate of the cell and ultimately, the tissue or organism, may well be determined by the genetic make-up of the individual and …”

Section: Discussionmentioning

confidence: 75%

“…Changes in the expression of oxidative stress also persisted. Both oxidative stress and miochondrial abnormalities have been suggested as important factors in the production of persistent, nonclonal genomic instability in cells (Clutton et al, 1996). This group showed that irradiated cells that survive have a persistently elevated production of toxic oxygen radicals.…”

Section: Discussionmentioning

confidence: 99%

“…On the basis of all these data, it now appears that the phenomenon of radiation induced genomic instability may in fact be induced by the bystander factor. A possible mechanism could involve an induction of a persistent oxidative stress response, as proposed by Clutton et al (1996), which can result in the production of reactive oxygen species (ROS) leading to oxidative damage (chromosome breaks/mutations). Persistent initiation of the apoptotic cascade through a relatively long-term change in mitochondrial membrane permeability would be consistent with findings by Lyng et al (1996) which showed persistent apoptosis in distant progeny of irradiated cells.…”

Section: Discussionmentioning

confidence: 99%

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Production of a signal by irradiated cells which leads to a response in unirradiated cells characteristic of initiation of apoptosis

Lyng¹,

Seymour²,

Mothersill³

2000

Br J Cancer

243

154

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Summary This study investigated the ability of medium from irradiated cells to induce early events in the apoptotic cascade, such as mobilization of intracellular calcium, loss of mitochondrial membrane potential and increase in reactive oxygen species, in cells which were never exposed to radiation. Medium from irradiated human keratinocytes was harvested and transferred to unirradiated keratinocytes. Endpoints characteristic of the initiation of apoptosis were monitored for a period of 24 h following medium transfer. Clonogenic survival was also measured. Rapid calcium fluxes (within 30 s), loss of mitochondrial membrane potential, increases in reactive oxygen species (from 6 h after medium transfer), an increase in the number of apoptotic cells (48 hours after medium transfer) and a marked reduction in clonogenic survival (after 9 days) were observed. There was no significant difference between medium generated by cells irradiated at 0.5 Gy or 5 Gy. The data suggest that initiating events in the apoptotic cascade were induced in unexposed cells by a signal produced by irradiated cells.

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Production of a signal by irradiated cells which leads to a response in unirradiated cells characteristic of initiation of apoptosis

Lyng¹,

Seymour²,

Mothersill³

2000

Br J Cancer

243

154

View full text Add to dashboard Cite

show abstract

“…Tissue/cells at treatment site (including tumor-associated endothelial cells, normal tissue and remnant cancer cells) that initially survive irradiation may elicit factors. These factor(s) may transduce and alter the physiology of the neighboring bystander cells [18][19][20][21][22] by paracrine feedback signaling that may pre-dispose the cells to carcinogenic processes [23] in normal tissue, and tumor cell growth in surviving cancer cells leading to tumor recurrence at later time. Reports from our laboratory demonstrated that radiation at doses used in fractionated radiotherapy could selectively induce the DNA-binding activity of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) [24][25][26] and the occurrence of a positive feedback loop between tumor necrosis factor-alpha (TNF-α) and NF-κB.…”

Section: Bystander Effectmentioning

confidence: 99%

Typical cell signaling response to ionizing radiation: DNA damage and extranuclear damage

2012

Chin. J. Cancer Res.

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To treat many types of cancer, ionizing radiation (IR) is primarily used as external-beam radiotherapy, brachytherapy, and targeted radionuclide therapy. Exposure of tumor cells to IR can induce DNA damage as well as generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) which can cause non-DNA lesions or extracellular damage like lipid perioxidation. The initial radiation-induced cell responses to DNA damage and ROS like the proteolytic processing, as well as synthesis and releasing ligands (such as growth factors, cytokines, and hormone) can cause the delayed secondary responses in irradiated and unirradiated bystander cells through paracrine and autocrine pathways.

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“…Furthermore, genomic instability is thought to be mediated via bystander mechanisms (43). Bystander effects have been shown to be mediated by gap-junction intercellular (GJIC) communication (41,44,45) and by signaling via diffusible secreted factors (46,47).…”

Section: Bystander Effectsmentioning

confidence: 99%

Challenges and progress in predicting biological responses to incorporated radioactivity

Howell¹,

Neti²,

Pinto³

et al. 2006

Radiation Protection Dosimetry

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Prediction of risks and therapeutic outcome in nuclear medicine largely rely on calculation of the absorbed dose. Absorbed dose specification is complex due to the wide variety of radiations emitted, nonuniform activity distribution, biokinetics, etc. Conventional organ absorbed dose estimates assumed that radioactivity is distributed uniformly throughout the organ. However, there have been dramatic improvements in dosimetry models that reflect the substructure of organs as well as tissue elements within them. These models rely on improved nuclear medicine imaging capabilities that facilitate determination of activity within voxels that represent tissue elements of about 0.2 -1 cm 3 . However, even these improved approaches assume that all cells within the tissue element receive the same dose. The tissue element may be comprised of a variety of cells having different radiosensitivities and different incorporated radioactivity. Furthermore, the extent to which nonuniform distributions of radioactivity within a small tissue element impact the absorbed dose distribution is strongly dependent on the number, type, and energy of the radiations emitted by the radionuclide. It is also necessary to know whether the dose to a given cell arises from radioactive decays within itself (self-dose) or decays in surrounding cells (cross-dose). Cellular response to selfdose can be considerably different than its response to cross-dose from the same radiopharmaceutical. Bystander effects can also play a role in the response. Evidence shows that even under conditions of "uniform" distribution of radioactivity, a combination of organ dosimetry, voxel dosimetry and dosimetry at the cellular and multicellular levels can be required to predict response.

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Radiation-induced genomic instability and persisting oxidative stress in primary bone marrow cultures

Cited by 245 publications

References 10 publications

Production of a signal by irradiated cells which leads to a response in unirradiated cells characteristic of initiation of apoptosis

Production of a signal by irradiated cells which leads to a response in unirradiated cells characteristic of initiation of apoptosis

Typical cell signaling response to ionizing radiation: DNA damage and extranuclear damage

Challenges and progress in predicting biological responses to incorporated radioactivity

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