The Impact of Individual In Vivo Repair of DNA Double-Strand Breaks on Oral Mucositis in Adjuvant Radiotherapy of Head-and-Neck Cancer

Fleckenstein, Jochen; Kühne, Martin; Seegmüller, Katharina; Derschang, Sarah; Melchior, Patrick; Gräber, Stefan; Fricke, Andreas; Rübe, Claudia E.; Rübe, Christian

doi:10.1016/j.ijrobp.2010.08.004

Cited by 46 publications

(40 citation statements)

References 24 publications

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“…Radiation therapy used in cancer treatment is applied either alone or in combination with chemotherapy; however, radiation therapy induces severe side-effects (acute effects such as erythema, edema, mucositis, dry or moist desquamation, severe skin changes, and late effects such as telangiectasia, fibrosis, cancer induction, brachial plexopathy, neurological effects) due to normal tissue toxicity (NTT) [81][82][83][84][85]. NTT has been graded by the Radiation Therapy Oncology Group into a standardized scale of acute and late responses after radiotherapy treatment for all tissue types, and these scales are used to avoid severe sequelae of radiotherapy [86].…”

Section: Peripheral Blood Mononuclear Cellsmentioning

confidence: 99%

“…gH2AX as a biomarker of toxicity and as a biodosimeter after systemic administration of radionuclide was investigated in vivo in several clinical studies [45,82]. For example, gH2AX induction and loss were assessed in a recent clinical study where radionuclide I 131 therapy for thyroid cancer was used [45].…”

Section: Cells/tissues Analyzedmentioning

confidence: 99%

“…It is also important to note that external irradiation treatment generally involves partial body irradiation whereas radionuclide therapy involves whole body exposure to irradiation. Another study showed that individuals who had higher levels of persistent gH2AX in PBMCs observed 24 h after in vivo exposure to X-rays (a single dose of 2 Gy, given once daily for 5 days per week) or RCT (radiotherapy in combination with chemotherapy) are likely to have an increased incidence of severe oral mucositis [82]. Following a CT examination, gH2AX levels in normal individuals reached baseline levels 24 h after the CT scan.…”

Section: Cells/tissues Analyzedmentioning

confidence: 99%

See 2 more Smart Citations

Persistent γH2AX: A promising molecular marker of DNA damage and aging

Siddiqui

François

Fenech

et al. 2015

Mutation Research/Reviews in Mutation Research

188

142

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Section: Peripheral Blood Mononuclear Cellsmentioning

confidence: 99%

Section: Cells/tissues Analyzedmentioning

confidence: 99%

Section: Cells/tissues Analyzedmentioning

confidence: 99%

See 1 more Smart Citation

Persistent γH2AX: A promising molecular marker of DNA damage and aging

Siddiqui

François

Fenech

et al. 2015

Mutation Research/Reviews in Mutation Research

188

142

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“…The uncertainties warrant further experimental analysis of the risk of radiation-induced diseases and complications during extended space flights. From experience in cancer therapy, we know that inflammation of the mucogingival membrane (oral mucositis) is a frequent complication of heavy-ion and X-ray radiotherapy (6)(7)(8)(9)(10)(11). Patients often complain about burning and intolerance of spicy foods, xerostomia, bacterial, fungal or viral infections, dental caries and loss of taste (12).…”

Section: Introductionmentioning

confidence: 99%

Carbon ions and X-rays induce pro-inflammatory effects in 3D oral mucosa models with and without PBMCs

et al. 2014

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Oral mucositis is a severe complication of radiotherapy. Hence, it may constitute a serious medical safety risk for astronauts during extended space flights, such as missions to Mars, during which they are exposed to heavy-ion irradiation. For risk assessment of developing radiation-induced mucositis, a three-dimensional (3D) organotypic oral mucosa model was irradiated with 12C heavy ions or X‑rays. The present study focused mainly on early radiation‑induced effects, such as the activation of nuclear factor κB (NFκB) and the expression or release of pro-inflammatory marker molecules. The 3D oral mucosa models with or without peripheral blood mononuclear cells (PBMCs) were irradiated with X‑rays or 12C heavy ions followed by snap freezing. Subsequently, cryosections were derived from the specimens, which were immunostained for analysis of compactness, DNA double strand breaks (DSB) and activation of NFκB. Radiation‑induced release of interleukin 6 (IL6) and interleukin 8 (IL8) was quantified by ELISA. Quantification of the DNA damage in irradiated mucosa models revealed distinctly more DSB after heavy-ion irradiation compared to X‑rays at definite time points, suggesting a higher gene toxicity of heavy ions. NFκB activation was observed after treatment with X‑rays or 12C particles. ELISA analyses showed significantly higher IL6 and IL8 levels after irradiation with X‑rays and 12C particles compared to non-irradiated controls, whereas co‑cultures including PBMCs released 2 to 3-fold higher interleukin concentrations compared to mucosa models without PBMCs. In this study, we demonstrated that several pro-inflammatory markers are induced by X‑rays and heavy-ion irradiation within an oral mucosa model. This suggests that oral mucositis indeed poses a risk for astronauts on extended space flights.

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“…The g-H2AX technique can distinguish between ATM2/2 homozygote and ATM6 heterozygote individuals 8 h after exposure of a blood sample to 1 Gy and has also been used to identify patients with solid tumours at a risk of adverse side effects because of impaired DNA repair [107]. g-H2AX measurement by flow cytometry has been shown by Bourton et al [108] to be a possible marker capable of predicting the risk of radiotherapy patients developing excessive normal tissue toxicity and to a lesser degree that may be used for the prediction of oral mucositis [109]. However, other studies show no correlation between g-H2AX foci and acute [110] or late tissue damage [111].…”

Section: Radiosensitivitymentioning

confidence: 99%

Deoxyribonucleic acid damage-associated biomarkers of ionising radiation: current status and future relevance for radiology and radiotherapy

Manning

Rothkamm²

2013

BJR

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Diagnostic and therapeutic radiation technology has developed dramatically in recent years, and its use has increased significantly, bringing clinical benefit. The use of diagnostic radiology has become widespread in modern society, particularly in paediatrics where the clinical benefit needs to be balanced with the risk of leukaemia and brain cancer increasing after exposure to low doses of radiation. With improving long-term survival rates of radiotherapy patients and the ever-increasing use of diagnostic and interventional radiology procedures, concern has risen over the long-term risks and side effects from such treatments. Biomarker development in radiology and radiotherapy has progressed significantly in recent years to investigate the effects of such use and optimise treatment. Recent biomarker development has focused on improving the limitations of established techniques by the use of automation, increasing sensitivity and developing novel biomarkers capable of quicker results. The effect of low-dose exposure (0-100 mGy) used in radiology, which is increasingly linked to cancer incidences, is being investigated, as some recent research challenges the linear-no-threshold model. Radiotherapy biomarkers are focused on identifying radiosensitive patients, determining the treatment-associated risk and allowing for a tailored and more successful treatment of cancer patients. For biomarkers in any of these areas to be successfully developed, stringent criteria must be applied in techniques and analysis of data to reduce variation among reports and allow data sets to be accurately compared. Newly developed biomarkers can then be used in combination with the established techniques to better understand and quantify the individual biological response to exposures associated with radiology tests and to personalise treatment plans for patients.

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The Impact of Individual In Vivo Repair of DNA Double-Strand Breaks on Oral Mucositis in Adjuvant Radiotherapy of Head-and-Neck Cancer

Cited by 46 publications

References 24 publications

Persistent γH2AX: A promising molecular marker of DNA damage and aging

Persistent γH2AX: A promising molecular marker of DNA damage and aging

Carbon ions and X-rays induce pro-inflammatory effects in 3D oral mucosa models with and without PBMCs

Deoxyribonucleic acid damage-associated biomarkers of ionising radiation: current status and future relevance for radiology and radiotherapy

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