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In JoVE (3)
- ΓH2AX foci के Ionising विकिरण करने के लिए प्रत्युत्तर में मात्रा का ठहराव
- ΓH2AX foci के ऊतकों के नमूनों में quantitation
- विकिरण के बाद γH2AX के स्थानिक वितरण का मूल्यांकन
Other Publications (4)
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Articles by Li-Jeen Mah in JoVE
JoVE General
ΓH2AX foci के Ionising विकिरण करने के लिए प्रत्युत्तर में मात्रा का ठहराव
1Epigenomic Medicine, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, 2Department of Pathology, The University of Melbourne, 3Epigenetics in Human Health and Disease, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct
डीएनए डबल भूग्रस्त एक आणविक मार्कर के रूप में γH2AX गठन का उपयोग धारियाँ की मात्रा का ठहराव विकिरण जीव विज्ञान में एक अमूल्य उपकरण बन गया है. यहाँ हम γH2AX foci के विकिरण के कक्षों के प्रदर्शन के बाद मात्रा का ठहराव के लिए एक immunofluorescence परख के उपयोग के प्रदर्शन.
JoVE General
ΓH2AX foci के ऊतकों के नमूनों में quantitation
1Epigenomic Medicine, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, 2Epigenetics in Human Health and Disease, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, 3Department of Pathology, The University of Melbourne, 4Department of Allergy and Immunology, Murdoch Children's Research Institute, Royal Children's Hospital, 5Department of Pediatrics, The University of Melbourne
डीएनए γH2AX foci के आधार पर डबल भूग्रस्त टूटता quantitation एक अमूल्य उपकरण बन गया है, ऊतक radiosensitivity और विकिरण संशोधित यौगिकों के प्रभाव के मूल्यांकन के लिए विकिरण जीव विज्ञान में, विशेष रूप से,. यहाँ हम γH2AX foci के ऊतकों के नमूनों में quantitation के लिए एक immunofluorescence परख का उपयोग प्रदर्शित करता है.
JoVE General
विकिरण के बाद γH2AX के स्थानिक वितरण का मूल्यांकन
1Epigenetics in Human Health and Disease, BakerIDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, 2Epigenomic Medicine, BakerIDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, 3Department of Pathology, University of Melbourne
ΓH2AX foci, जो Ser-139 H2AX के डीएनए डबल भूग्रस्त टूटता है के जवाब में phosphorylation निम्नलिखित फार्म का सूक्ष्म विश्लेषण विकिरण जीव विज्ञान में एक अमूल्य उपकरण बन गया है. यहाँ हम मोनो - methylated histone H3 सक्रिय transcribing euchromatin के एक epigenetic मार्कर के रूप में 4 lysine पर एक एंटीबॉडी का इस्तेमाल किया, नाभिक के भीतर विकिरण प्रेरित γH2AX गठन के स्थानिक वितरण का मूल्यांकन.
Other articles by Li-Jeen Mah on PubMed
GammaH2AX As a Molecular Marker of Aging and Disease
Double-strand breaks are one of the most critical DNA lesions with respect to cell-death and preservation of genomic integrity. Rapid phosphorylation of the histone variant H2AX at Ser-139 to form gammaH2AX is an early cellular response to DNA double-strand breaks. Visualization of discrete gammaH2AX foci using immunofluorescence-based assays has provided a sensitive and effective method for detecting DSBs which may be implicated in various pathologies including cancer, age-related diseases, chronic inflammatory diseases and ischemia-reperfusion injury. In this review, the potential utility and significance of gammaH2AX as a molecular marker of aging and disease is analysed.
Double-strand Breaks and the Concept of Short- and Long-term Epigenetic Memory
Double-strand breaks represent an extremely cytolethal form of DNA damage and thus pose a serious threat to the preservation of genetic and epigenetic information. Though it is well-known that double-strand breaks such as those generated by ionising radiation are among the principal causative factors behind mutations, chromosomal aberrations, genetic instability and carcinogenesis, significantly less is known about the epigenetic consequences of double-strand break formation and repair for carcinogenesis. Double-strand break repair is a highly coordinated process that requires the unravelling of the compacted chromatin structure to facilitate repair machinery access and then restoration of the original undamaged chromatin state. Recent experimental findings have pointed to a potential mechanism for double-strand break-induced epigenetic silencing. This review will discuss some of the key epigenetic regulatory processes involved in double-strand break (DSB) repair and how incomplete or incorrect restoration of chromatin structure can leave a DSB-induced epigenetic memory of damage with potentially pathological repercussions.
Evaluation of the Efficacy of Radiation-modifying Compounds Using γH2AX As a Molecular Marker of DNA Double-strand Breaks
Radiation therapy is a widely used therapeutic approach for cancer. To improve the efficacy of radiotherapy there is an intense interest in combining this modality with two broad classes of compounds, radiosensitizers and radioprotectors. These either enhance tumour-killing efficacy or mitigate damage to surrounding non-malignant tissue, respectively. Radiation exposure often results in the formation of DNA double-strand breaks, which are marked by the induction of H2AX phosphorylation to generate γH2AX. In addition to its essential role in DDR signalling and coordination of double-strand break repair, the ability to visualize and quantitate γH2AX foci using immunofluorescence microscopy techniques enables it to be exploited as an indicator of therapeutic efficacy in a range of cell types and tissues. This review will explore the emerging applicability of γH2AX as a marker for monitoring the effectiveness of radiation-modifying compounds.
Utility of γH2AX As a Molecular Marker of DNA Double-Strand Breaks in Nuclear Medicine: Applications to Radionuclide Therapy Employing Auger Electron-Emitting Isotopes
There is an intense interest in the development of radiopharmaceuticals for cancer therapy. In particular, radiopharmaceuticals which involve targeting radionuclides specifically to cancer cells with the use of monoclonal antibodies (radioimmunotherapy) or peptides (targeted radiotherapy) are being widely investigated. For example, the ultra-short range Auger electron-emitting isotopes, which are discussed in this review, are being considered in the context of DNAtargeted radiotherapy. The efficient quantitative evaluation of the levels of damage caused by such potential radiopharmaceuticals is required for assessment of therapeutic efficacy and determination of relevant doses for successful treatment. The DNA double-strand break surrogate marker, γH2AX, has emerged as a useful biomonitor of damage and thus effectiveness of treatment, offering a highly specific and sensitive means of assessment. This review will cover the potential applications of γH2AX in nuclear medicine, in particular radionuclide therapy.
