Radiation-induced DNA damage and delayed induced genomic instability

Suzuki, Keiji; Ojima, Mitsuaki; Kodama, Seiji; Watanabe, Masami

doi:10.1038/sj.onc.1206881

Cited by 150 publications

(81 citation statements)

References 76 publications

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“…DSBs represent the most challenging type of DNA damage (Suzuki et al, 2003). A failure to rejoin DSBs leads to cell death, whereas joining of DNA ends originating from different DSBs results in structural chromosome rearrangements.…”

Section: Introductionmentioning

confidence: 99%

Chromatin mobility is increased at sites of DNA double-strand breaks

Krawczyk¹,

Borovski²,

Stap³

et al. 2012

Journal of Cell Science

132

146

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SummaryDNA double-strand breaks (DSBs) can efficiently kill cancer cells, but they can also produce unwanted chromosome rearrangements when DNA ends from different DSBs are erroneously joined. Movement of DSB-containing chromatin domains might facilitate these DSB interactions and promote the formation of chromosome rearrangements. Therefore, we analyzed the mobility of chromatin domains containing DSBs, marked by the fluorescently tagged DSB marker 53BP1, in living mammalian cells and compared it with the mobility of undamaged chromatin on a time-scale relevant for DSB repair. We found that chromatin domains containing DSBs are substantially more mobile than intact chromatin, and are capable of roaming a more than twofold larger area of the cell nucleus. Moreover, this increased DSB mobility, but not the mobility of undamaged chromatin, can be reduced by agents that affect higher-order chromatin organization.

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Section: Introductionmentioning

confidence: 99%

Chromatin mobility is increased at sites of DNA double-strand breaks

Krawczyk¹,

Borovski²,

Stap³

et al. 2012

Journal of Cell Science

132

146

View full text Add to dashboard Cite

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“…In vitro studies on cells to date revealed that ionizing radiation may induce many effects like: metabolism changes [48], cell cycle delay [19], DNA damage [47], cell membrane damage [4] and, finally, apoptotic or necrotic death [49]. The present study reports the variation in the 1 H-NMR visible mobile lipids that occurred in C6 cells after the X-ray irradiation and incubation.…”

Section: Discussionmentioning

confidence: 91%

Original article High resolution proton nuclear magnetic resonance (1H NMR) spectroscopy of surviving C6 glioma cells after X-ray irradiation

Matulewicz¹,

Cichoń²,

Sokół³

et al. 2013

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A b s t r a c t (24, 48, 72 and 96 hours) P Pu ur rp po os se e: : To study biochemical response of living model of glioma to X-rays irradiation using high resolution proton nuclear magnetic resonance ( 1 H NMR) spectroscopy. M Ma at te er ri ia al l a an nd d m me et th ho od ds s: : Rat glioma C6 cells were irradiated with 3.8 Gy (D 0 , the 37% clonogenic survival dose) of X-rays from a teletherapy unit at the dose rate 8.8 Gy/min. After irradiation the cells were incubated at 37°C/5%CO 2 /95%O 2 for various period of incubation

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“…The prime tenet of therapeutic radiobiology involves the use of ionizing radiation to induce double-strand DNA breakage. This breakage, above all else, leads to errors during DNA replication that cause immediate cell death, or so-called ''delayed induced genomic instability,'' which is observed as decreased viability for up to several generations after the initial radiologic insult (21). However, if cells are somehow induced to slow or even stop replication, then radiationinduced cell death would be, at the very least, negatively affected.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Evaluation of Radioprotective and Radiosensitizing Effects of Rituximab

Kapadia¹,

Engles²,

Wahl³

2008

J Nucl Med

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Clinical radioimmunotherapies with anti-CD20 monoclonal antibodies involve administering a predose of unlabeled anti-CD20 antibodies to favorably alter the biodistribution profile of the subsequently administered radiolabeled antibodies and mediate antitumor effects. Prior in vitro data suggested that unlabeled anti-CD20 monoclonal antibodies radiosensitize lymphoma cells as well. We assessed the antiproliferative and possible radiosensitizing capabilities of an anti-CD20 monoclonal antibody, rituximab. Methods: Luciferase-transfected (via a lentivirus vector) CD20 1 human Raji lymphoma cells in log-phase growth were incubated with or without rituximab (20 mg/mL) for either 1 or 24 h before external-beam radiation exposure. Cell counts were measured with a luciferase assay at 24-h intervals. Subsets of these cells were also analyzed for cell cycle status by flow cytometry. Results: Rituximab pretreatment and irradiation were found to significantly inhibit tumor cell growth compared with irradiation alone (by a factor of 0.40 at 1 Gy [P , 0.01]). One hour of rituximab pretreatment modestly radiosensitized tumor cells at a radiation dose of 1 Gy (by a factor of 1.03 compared with the results for nonirradiated cells). At higher radiation doses (2 and 12 Gy), 1 h of rituximab pretreatment paradoxically radioprotected tumor cells by factors of 0.25 (P , 0.01) and 0.54 (P , 0.05), respectively. Rituximab predosing for 24 h was found to be radiosensitizing at a radiation dose of 4 Gy (by a factor of 2.84 [P , 0.01]) but radioprotective at radiation doses of 1, 8, and 12 Gy (by factors of 0.10 [P , 0.01], 2.50 [P , 0.01], and 2.07 [P , 0.05], respectively). These results correlated with retardation of the cell cycle at 6 d after rituximab administration, as determined by flow cytometry. Conclusion: Rituximab demonstrated a direct tumor antiproliferative effect in the absence of radiation. At lower levels of radiation exposure, rituximab radiosensitized Raji lymphoma cells. At higher doses of radiation, rituximab paradoxically protected tumor cells against ionizing radiation, possibly through effects on the cell cycle. These radiobiologic effects of rituximab should be carefully considered in the design of radioimmunotherapeutic trials.

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Radiation-induced DNA damage and delayed induced genomic instability

Cited by 150 publications

References 76 publications

Chromatin mobility is increased at sites of DNA double-strand breaks

Chromatin mobility is increased at sites of DNA double-strand breaks

Original article High resolution proton nuclear magnetic resonance (1H NMR) spectroscopy of surviving C6 glioma cells after X-ray irradiation

In Vitro Evaluation of Radioprotective and Radiosensitizing Effects of Rituximab

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