DNA double-strand break repair defects in syndromes associated with acute radiation response: At least two different assays to predict intrinsic radiosensitivity?

Joubert, Aurélie; Zimmerman, Kristin; Bencokova, Zuzana; Gastaldo, Jérôme; Chavaudra, N.; Favaudon, Vincent; Arlett, C.F.; Foray, Nicolas

doi:10.1080/09553000701797039

Cited by 106 publications

(134 citation statements)

References 62 publications

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“…The immunofluorescence protocol employed for DNA repair and signaling factors was described elsewhere [30,31]. Anti-pH2AX ser139 antibodies (Euromedex) were used at 1:800.…”

Section: Immunofluorescencementioning

confidence: 99%

Genotoxicity of acute and chronic gamma‐irradiation on zebrafish cells and consequences for embryo development

Pereira

Bourrachot

Cavalié

et al. 2011

Enviro Toxic and Chemistry

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The effects of radiation on biological systems have been studied for many years, and it is now accepted that direct damage to DNA from radiation is the triggering event leading to biological effects. In the present study, DNA damage induced by acute or chronic irradiation was compared at the cellular (zebrafish [Danio rerio] cell line ZF4) and developmental (embryo) levels. Zebrafish ZF4 cells and embryos (at 3 h postfertilization) were exposed within ranges of acute doses (0.3-2 Gy/d) or chronic dose rates (0.1-0.75 Gy/d). DNA damage was assessed by immunodetection of γ-H2AX and DNA-PK (DNA double-strand breaks) and the alkaline comet assay (DNA single-strand breaks). Zebrafish embryo development and DNA damage were examined after 120 h. At low doses, chronic irradiation induced more residual DNA damage than acute irradiation, but embryo development was normal. From 0.3 Gy, a hyper-radiosensitivity phenomenon compared to other species was shown for acute exposure with an increase of DNA damage, an impairment of hatching success, and larvae abnormalities. These results suggest a dose-dependent correlation between unrepaired DNA damage and abnormalities in embryo development, supporting the use of DNA repair proteins as predictive biomarkers of ionizing radiation exposure. This could have important implications for environmental protection.

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“…The immunofluorescence protocol employed for DNA repair and signaling factors was described elsewhere [30,31]. Anti-pH2AX ser139 antibodies (Euromedex) were used at 1:800.…”

Section: Immunofluorescencementioning

confidence: 99%

Genotoxicity of acute and chronic gamma‐irradiation on zebrafish cells and consequences for embryo development

Pereira

Bourrachot

Cavalié

et al. 2011

Enviro Toxic and Chemistry

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“…This DSB repair pathway is dependent on the ATM kinase activity that may be considered as the major DNA-breaking stress signaling pathway in mammalians. The inhibition of NHEJ may be rescued by other repair pathways, like the RAD51-and/or MRE11-dependent recombination process (Dudas and Chovanec, 2004;Joubert et al, 2008). Interestingly, these last two recombination pathways were shown to require a functional BRCA1 protein, a tumor suppressor whose mutations are responsible for inherited breast cancers (Scully et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

DNA Double-Strand Breaks Repair and Signaling of Human Gliomas and Normal Brain Cells in Response to Radiation: Potential Impact of the ATM-and BRCA1- Dependent Pathways

Granzotto¹,

Bencokova²,

Vogin³

et al. 2011

Brain Tumors - Current and Emerging Therapeutic Strategies

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“…Since the induction of DNA damage is thought to be a primary mode of action of adriamycin (5), we evaluated the effects of adriamycin alone as well as with sildenafil, on gamma H2AX formation, a well established indicator of DNA damage (6). Figure 2 indicates that sildenafil failed to modify the extent of damage, which is again consistent with the lack of attenuation of drug sensitivity.…”

Section: Studies In Breast Tumor Cellsmentioning

confidence: 50%

Sildenafil and Phosphofiesterase-5 Inhibitors to Reduce Cardiotoxicity and Enhance the Response of Breast Tumors to Doxrubicin

Gewirtz¹

2008

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Department of Defense, Washington Headquarters Services, Directorate for Information SPONSOR/MONITOR'S REPORT NUMBER(S) DISTRIBUTION / AVAILABILITY STATEMENTApproved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES ABSTRACTIn our studies of the interaction between sildenafil and adriamycin in breast tumor cells and cardiomyocytes, we have made the following observations. In breast tumor cells: 1. Sildenafil fails to protect various breast tumor cell lines against the toxicity of adriamycin. 2. Sildenafil moderately enhances the response to adriamycin in breast tumor cells .3. Sildenafil does not alter the extent of DNA damage induced by adriamycin in breast tumor cells. 4. Adriamycin promotes autophagy in breast tumor cells. 5. Sildenafil appears to increase sensitivity to irradiation in breast tumor cells. In cardiomyocytes: 1. Questions are raised relating to the role of reactive oxygen in the cardiotoxicity of adriamycin. 2. The combination of Herceptin with taxol or adriamycin is relatively toxic in cardiomyocytes. Based on these observations, we propose to further explore the basis for adriamycin cardiotoxicity as well as examining the capacity of sildenafil to protect the heart cells from the combination of Herceptin with Adriamycin and with taxol. We will evaluate the influence of sildenafil on autophagy and senescence in both breast tumor cells and cardiomyocytes. We will pursue the unexpected finding that sildenafil appears to increase sensitivity to radiation in the breast tumor cells by attempting to understand the mechanistic basis for this observation. We will also assess the impact of sildenafil on radiation sensitivity in the cardiomyocyte. These proposed studies are of significance because the heart is known to incur damage during irradiation of the breast during therapy for breast cancer.

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DNA double-strand break repair defects in syndromes associated with acute radiation response: At least two different assays to predict intrinsic radiosensitivity?

Cited by 106 publications

References 62 publications

Genotoxicity of acute and chronic gamma‐irradiation on zebrafish cells and consequences for embryo development

Genotoxicity of acute and chronic gamma‐irradiation on zebrafish cells and consequences for embryo development

DNA Double-Strand Breaks Repair and Signaling of Human Gliomas and Normal Brain Cells in Response to Radiation: Potential Impact of the ATM-and BRCA1- Dependent Pathways

Sildenafil and Phosphofiesterase-5 Inhibitors to Reduce Cardiotoxicity and Enhance the Response of Breast Tumors to Doxrubicin

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