Histological and biochemical analysis of DNA damage after BNCT in rat model

Masutani, Mitsuko; Baiseitov, Diaz; Itoh, Tasuku; Hirai, Takahisa; Berikkhanova, Kulzhan; Murakami, Yasufumi; Zhumadilov, Zhaxybay; Imahori, Yoshio; Hoshi, Masaharu; Itami, Jun

doi:10.1016/j.apradiso.2014.03.003

Cited by 18 publications

(16 citation statements)

References 19 publications

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“…Rittinghousen et al [2013] found about 150 positive nuclei per mm 2 in the lung of female Wistar rats, while urinary bladder of 5‐week‐old F344 rats showed approximately 2 γ‐H2AX‐positive nuclei per 1000 cells counted [Toyoda et al, ]. Finally, no cell with the γ‐H2AX signal or a very slight amount of nuclei was found in the brain of Wistar rats developing lymphosarcomas [Masutani et al, ] or in the duodenum of B6C3F1 mice, respectively [Thompson et al, ].…”

Section: Discussionmentioning

confidence: 99%

Increased level of DNA damage in some organs of obese Zucker rats by γ‐H2AX analysis

Azzarà

Chiaramonte

Filomeni

et al. 2017

Environ and Mol Mutagen

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In a recent study, we showed that lymphocytes of obese Italian children/adolescents displayed levels of double strand breaks (DSB), assayed as serine 139-phosphorylated histone H2AX (γ-H2AX), about eightfold higher than normal weight controls, and that 30% of this damage-generated micronuclei. These findings suggested that obese children could be at increased risk of obesity-mediated cancer later in life. We therefore aimed to assess the level of γ-H2AX in a genetic animal model of obesity (Zucker rat) to identify a genotoxic/carcinogenic risk in some organs. The DSB marker was studied in 3- to 4-week-old rats and in 9- to 13-week-old rats. Paraffin-embedded sections of heart, thyroid, liver, pancreas, lung, kidney, esophagus, and gut from the fa-/fa- (obese) and the fa+/fa- (lean) control animals were processed for immunohistochemistry detection of γ-H2AX. Pancreas (0.0624 ± 0.0195), lung (0.1197 ± 0.0217), esophagus (0.1230 ± 0.0351), kidney (0.1546 ± 0.0149), and gut (0.1724 ± 0.0352) of 9- to 13-week-old obese rats showed a higher proportion of γ-H2AX-positive nuclei, than their lean counterparts (0.0092 ± 0.0033, 0.0416 ± 0.0185, 0.0368 ± 0.0088, 0.0686 ± 0.0318, and 0.0703 ± 0.0239, respectively). No difference was seen in the 3- to 4-week-old age group with regard to obesity, indicating that the DNA damage increased with older age of the rats. We hypothesize that the organs of the obese animals showing high levels of DSB could represent target tissues for the development of obesity-related cancers. Environ. Mol. Mutagen. 58:477-484, 2017. © 2017 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

Increased level of DNA damage in some organs of obese Zucker rats by γ‐H2AX analysis

Azzarà

Chiaramonte

Filomeni

et al. 2017

Environ and Mol Mutagen

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“…As far as we know, no extensive genomic or transcriptomic studies have been performed to evaluate the changes in the transcription that is induced by this treatment. A preliminary study focused on the DNA damage induced by irradiation while using a rat tumor graft model [18]; this work followed the levels of some proteins by means of western blotting and showed an upregulation of High mobility group box 1 (HMGB1), a nuclear protein involved in necrosis and inflammation processes, which was proposed as an early diagnostic marker. Surely, for the study of the effects of BNCT, proteomics is a promising tool, which has already been applied in an in vitro study on the effects of mercaptoundecahydrododecaborate (BSH) on phospholipid hydroperoxide glutathione peroxidase [19]; in this case, a gel-based approach was used to separate the native protein from the protein that was covalently bound to BSH, which were then characterized by means of liquid chromatography coupled to mass spectrometry (LC-MS).…”

Section: Introductionmentioning

confidence: 99%

Urinary Proteomics Profiles Are Useful for Detection of Cancer Biomarkers and Changes Induced by Therapeutic Procedures

et al. 2019

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Boron neutron capture therapy (BNCT) is a binary cancer treatment modality where two different agents (10B and thermal neutrons) have to be present to produce an effect. A dedicated trial design is necessary for early clinical trials. The concentration of 10B in tissues is an accepted surrogate to predict BNCT effects on tissues. Tissue, blood, and urines were sampled after infusion of two different boron carriers, namely BSH and BPA in the frame of the European Organisation for Research and Treatment of Cancer (EORTC) trial 11001. In this study, urine samples were used to identify protein profiles prior and after drug infusion during surgery. Here, an approach that is based on the mass spectrometry (MS)-based proteomic analysis of urine samples from head and neck squamous cell carcinoma (HNSCC) and thyroid cancer patients is presented. This method allowed the identification of several inflammation- and cancer-related proteins, which could serve as tumor biomarkers. In addition, changes in the urinary proteome during and after therapeutic interventions were detected. In particular, a reduction of three proteins that were involved in inflammation has been observed: Galectin-3 Binding Protein, CD44, and osteopontin. The present work represents a proof of principle to follow proteasome changes during complex treatments based on urine samples.

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“…This is the case of the study by Rodriguez et al [50], which determined that the number of localized lesions was lower when comparing gamma-ray radiation with neutron or BNCT radiation, but the damage caused by BNCT was densely concentrated in clusters, which correlates with the expected more complex damage caused by high LET radiation. Moreover, these large foci lesions were persistent when observed for longer timeframes, describing firm or irreparable long-term damage [47,48]. Thus, despite an initial lower γH2AX foci count, the BNCT DNA damage profile involves more complex and irreparable damage patterns that would mean a higher radiobiological effect.…”

Section: Bnct Biological Dosimetrymentioning

confidence: 99%

Physical Bases of Boron Neutron Capture Therapy, Dosimetry, and Its Mechanisms of Action—A Critical Overview of the Literature

Skwierawska¹,

Balcerzyk²,

López-Valverde³

et al. 2021

Preprint

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The success of boron neutron capture therapy (BNCT) depends mainly on sufficient spatial biodistribution of boron (B-10) localized around or within neoplastic cells to produce a high dose gradient between the tumor and healthy tissue. Contrary to what is usual in radiotherapy, BNCT proposes treatment planning directed at the cell rather than the tumor mass. However, it is not yet possible to precisely determine the concentration of B-10 in a specific tissue in real-time using non-invasive methods. Some critical issues still need to be resolved if BNCT is to become a valuable, minimally invasive, and efficient cancer treatment. This review article provides an overview of the funda-mental principles, recent advances, and future directions of BNCT as a cell-targeted cancer therapy. The main emphasis is on topics related to biological dosimetry, methods for assessing boron concentration, mechanisms of action of BNCT, and its physical bases for clinical implementation.

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Histological and biochemical analysis of DNA damage after BNCT in rat model

Cited by 18 publications

References 19 publications

Increased level of DNA damage in some organs of obese Zucker rats by γ‐H2AX analysis

Increased level of DNA damage in some organs of obese Zucker rats by γ‐H2AX analysis

Urinary Proteomics Profiles Are Useful for Detection of Cancer Biomarkers and Changes Induced by Therapeutic Procedures

Physical Bases of Boron Neutron Capture Therapy, Dosimetry, and Its Mechanisms of Action—A Critical Overview of the Literature

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