Induction of lethal bystander effects in human breast cancer cell cultures by DNA-incorporated Iodine-125 depends on phenotype

Akudugu, John; Azzam, Edouard I.; Howell, Roger W.

doi:10.3109/09553002.2012.683511

Cited by 20 publications

(28 citation statements)

References 40 publications

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“…In contrast, other studies with human cells exposed to low doses of sparsely ionizing radiations suggested that junctional communication enhances the expression of protective effects against clastogenic and lethal damages [23, 24]. Together, the studies support the concept that the nature of the effects of junctional communication in response to irradiation or other toxic agents greatly depend on the type and dose of the stressful agent, the biochemical change produced in the targeted cells and the genotype and/or phenotype of the targeted and bystander cells [5, 25, 26]. Depending on connexin, gap junction channels mediate the propagation of biochemical signals that either enhance or mitigate stressful effects in targeted cells, and in some cases result in important biological changes in non-targeted cells in the vicinity that can persist over multiple cellular divisions (reviewed in [27, 28]).…”

Section: Introductionmentioning

confidence: 81%

Human cell responses to ionizing radiation are differentially affected by the expressed connexins

Autsavapromporn

Toledo

Jay‐Gerin

et al. 2012

Journal of Radiation Research

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In multicellular organisms, intercellular communication is essential for homeostatic functions and has a major role in tissue responses to stress. Here, we describe the effects of expression of different connexins, which form gap junction channels with different permeabilities, on the responses of human cells to ionizing radiation. Exposure of confluent HeLa cell cultures to 137Cs γ rays, 3.7 MeV α particles, 1000 MeV protons or 1000 MeV/u iron ions resulted in distinct effects when the cells expressed gap junction channels composed of either connexin26 (Cx26) or connexin32 (Cx32). Irradiated HeLa cells expressing Cx26 generally showed decreased clonogenic survival and reduced metabolic activity relative to parental cells lacking gap junction communication. In contrast, irradiated HeLa cells expressing Cx32 generally showed enhanced survival and greater metabolic activity relative to the control cells. The effects on clonogenic survival correlated more strongly with effects on metabolic activity than with DNA damage as assessed by micronucleus formation. The data also showed that the ability of a connexin to affect clonogenic survival following ionizing radiation can depend on the specific type of radiation. Together, these findings show that specific types of connexin channels are targets that may be exploited to enhance radiotherapeutic efficacy and to formulate countermeasures to the harmful effects of specific types of ionizing radiation.

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Section: Introductionmentioning

confidence: 81%

Human cell responses to ionizing radiation are differentially affected by the expressed connexins

Autsavapromporn

Toledo

Jay‐Gerin

et al. 2012

Journal of Radiation Research

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“…Inhibitory bystander effects were also observed with 125 I-UdR in vitro in chinese hamster V79 cells (85), in colon cancer cells (86) and in the breast cancer cell line MCF7 (84). However, in another breast cancer cell line (MDA-MB-231) no bystander effects were observed indicating that differences in the phenotypes of cells also could play a role in the induction of bystander effects (87). In vivo experiments using human colon carcinoma cells, labeled with a lethal dose of 125 I-UdR prior to mixing with unlabeled cells and before injection into nude mice showed a significant inhibitory effect on tumor growth due to bystander effects in the non-labeled cells (88).…”

Section: Bystander Effectsmentioning

confidence: 92%

Novel radioisotope-based nanomedical approaches

Olsen¹,

Thisgaard²,

Vogel

et al. 2013

European Journal of Nanomedicine

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Radioisotope therapy of cancer is on the rise applying mainly β-emitting radionuclides. However, due to exposure of healthy tissues, the maximum achievable radiation dose with these is limited. Auger-electron emitters (AEs) represent a promising alternative because of their mode of decay within a short nanometer range. The challenge is that their therapeutic efficacy relies on a close vicinity to DNA. To overcome this and to minimize toxicity, the construction of smart nanomedical devices is required, which ascertain tumor cell targeting with succeeding cellular uptake and nuclear translocation. In this review we describe the potential of AEs with focus on their delivery down to the DNA level and their cellular effects. Reported efforts comprise different tumor-targeting strategies, including the use of antibodies or peptides with nuclear localizing sequences. Recently, attention has shifted to various nanoparticle formats for overcoming delivery problems. To this end, these approaches have mostly been tested in cell lines in vitro applying AEs more suited for imaging than therapy. This defines a demand for nanomedical formulations with documented in vivo activity, using AEs selected for their therapeutic potential to come closer to real clinical settings.

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“…However, it cannot be excluded that DNA/ 125 IUDR or other radioactive molecular products released from damaged cells can additionally target neighbor cells directly, although this possibility is not considered by authors. The secretion of radiolabeled DNA derivatives resulting from damaged cells could be probably partly responsible for the different ability of various cells to induce a bystander effect observed by Akadugu et al [59]. In the studies performed on human breast carcinoma MDA-MB-231 or MCF-7 cells using 3-D cell culture on carbon scaffold they demonstrated the capacity of 125 IUdR to induce lethal bystander effects in human breast cancer cells MCF-7 line but not in MDA-MB-231 cell line indicating that the bystander response is cell type dependent.…”

Section: In Vitro Studies Of Radionuclide Induced Bystander Effectmentioning

confidence: 99%

Radionuclides in radiation-induced bystander effect; may it share in radionuclide therapy?

Wideł¹

2017

neo

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For many years in radiobiology and radiotherapy predominated the conviction that cellular DNA is the main target for ionizing radiation, however, the view has changed in the past 20 years. Nowadays, it is assumed that not only directed (targeted) radiation effect, but also an indirect (non-targeted) effect may contribute to the result of radiation treatment. Non-targeted effect is relatively well recognized after external beam irradiation in vitro and in vivo, and comprises such phenomena like radiation-induced bystander effect (RIBE), genomic instability, adaptive response and abscopal (out of field) effect. These stress-induced and molecular signaling mediated phenomena appear in non-targeted cells as variety responses resembling that observed in directly hit cells. Bystander effects can be both detrimental and beneficial in dependence on dose, dose-rate, cell type, genetic status and experimental condition. Less is known about radionuclide-induced non-targeted effects in radionuclide therapy, although, based on characteristics of the radionuclide radiation, on experiments in vitro utilizing classical and 3-D cell cultures, and preclinical study on animals it seems obvious that exposure to radionuclide is accompanied by various bystander effects, mostly damaging, less often protective. This review summarizes existing data on radionuclide induced bystander effects comprising radionuclides emitting beta- and alpha-particles and Auger electrons used in tumor radiotherapy and diagnostics. So far, separation of the direct effect of radionuclide decay from crossfire and bystander effects in clinical targeted radionuclide therapy is impossible because of the lack of methods to assess whether, and to what extent bystander effect is involved in human organism. Considerations on this topic are also included.

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Induction of lethal bystander effects in human breast cancer cell cultures by DNA-incorporated Iodine-125 depends on phenotype

Cited by 20 publications

References 40 publications

Human cell responses to ionizing radiation are differentially affected by the expressed connexins

Human cell responses to ionizing radiation are differentially affected by the expressed connexins

Novel radioisotope-based nanomedical approaches

Radionuclides in radiation-induced bystander effect; may it share in radionuclide therapy?

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