Effects of Ionizing Radiation in Targeted and Nontargeted Cells

Iyer, Rashi; Lehnert, Bruce E.

doi:10.1006/abbi.1999.1684

Cited by 103 publications

(65 citation statements)

References 116 publications

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“…Most of the studies on radiation-induced bystander effects have been performed with in vitro cell culture models (Iyer and Lehnert, 2000a). The aim of this approach was to test the role of bystander response in an in vivo-like multicellular system using a microbeam technique for targeting individual cells.…”

Section: Discussionmentioning

confidence: 99%

A proliferation-dependent bystander effect in primary porcine and human urothelial explants in response to targeted irradiation

Belyakov

Folkard

Mothersill³

et al. 2003

Br J Cancer

104

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The aim of this study was to test whether radiation-induced bystander effects are involved in the response of multicellular systems to targeted irradiation. A primary explant technique was used that reconstructed the in vivo microarchitecture of normal urothelium with proliferating and differentiated cells present. Sections of human and porcine ureter were cultured as explants and irradiated on day 7 when the urothelial outgrowth formed a halo around the tissue fragment. The Gray Cancer Institute charge particle microbeam facility allowed the irradiation of individual cells within the explant outgrowth with a predetermined exact number of 3 He 2+ ions (which have very similar biological effectiveness to a-particles). A total of 10 individual cell nuclei were irradiated with 10 3 He 2+ ions either on the periphery, where proliferating cells are located, or at the centre of the explant outgrowth, which consisted of terminally differentiated cells. Samples were fixed 3 days after irradiation, stained and scored. The fraction of apoptotic and micronucleated cells was measured and a significant bystander-induced damage was observed. Approximately 2000 -6000 cells could be damaged by the irradiation of a few cells initially, suggesting a cascade mechanism of cell damage induction. However, the fraction of micronucleated and apoptotic cells did not exceed 1 -2% of the total number of the cells within the explant outgrowth. It is concluded that the bystander-induced damage depends on the proliferation status of the cells and can be observed in an in vitro explant model.

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Section: Discussionmentioning

confidence: 99%

A proliferation-dependent bystander effect in primary porcine and human urothelial explants in response to targeted irradiation

Belyakov

Folkard

Mothersill³

et al. 2003

Br J Cancer

104

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“…One mechanism seems dependent on gap-junction intercellular communication stimulating a damage-signalling pathway mediated by the tumour suppressor gene product p53 (Azzam et al, 1998(Azzam et al, , 2001. Other studies implicate a second mechanism in which irradiated cells secrete cytokines such as TGF-b or IL-8 or other factors that act to increase intracellular levels of ROS in unirradiated cells (Lehnert and Goodwin, 1997a, b;Narayanan et al, 1997;Iyer and Lehnert, 2000).…”

Section: Mechanisms Underlying Radiation-induced Bystander Effectsmentioning

confidence: 99%

Radiation-induced genomic instability and bystander effects: inter-related nontargeted effects of exposure to ionizing radiation

2003

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“…During the last decade several studies appeared about cytotoxic 'bystander' effects in irradiated cell cultures (reviewed by Iyer and Lehnert, 2000). Cytotoxic and clastogenic effects were detected on nonirradiated cells in contact with irradiated cells or exchanged via the culture medium (Hallahan et al, 1989;Mothersill and Seymour, 1997;Bishayee et al, 2001; Lewis et al, 2001;Sawant et al, 2002).…”

mentioning

confidence: 99%

Changes in the ornithine cycle following ionising radiation cause a cytotoxic conditioning of the culture medium of H35 hepatoma cells

et al. 2003

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Cultured H35 hepatoma cells release a cytotoxic factor in response to irradiation with X-rays. When the conditioned medium from irradiated cells is given to nonirradiated cells, growth is inhibited and followed by cell death, possibly apoptosis, Analysis of the conditioned medium reveals a dramatic change in the ornithine (urea) cycle components after the irradiation. A strong decrease in medium arginine is accompanied with parallel increases in ornithine, citrulline and ammonia. The high level of ammonia appears to be largely responsible for the observed cytotoxicity. The development of hyperammonia by irradiated cells and the related toxicity depend on the radiation dose and the number of cells seeded thereafter for the medium conditioning. Development of cytotoxicity by irradiated cells is completely prevented with the arginase inhibitor L-norvaline, in arginine-deficient medium or when citrulline replaces arginine. These preventive measures result in subtoxic ammonia levels.

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Effects of Ionizing Radiation in Targeted and Nontargeted Cells

Cited by 103 publications

References 116 publications

A proliferation-dependent bystander effect in primary porcine and human urothelial explants in response to targeted irradiation

A proliferation-dependent bystander effect in primary porcine and human urothelial explants in response to targeted irradiation

Radiation-induced genomic instability and bystander effects: inter-related nontargeted effects of exposure to ionizing radiation

Changes in the ornithine cycle following ionising radiation cause a cytotoxic conditioning of the culture medium of H35 hepatoma cells

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