Abstract
The past year has seen considerable developments in the use of the DNA double-strand breaks (DSBs) to evaluate genome alterations in cells undergoing a variety of genotoxic stresses in vitro and in vivo. When the γ-H2AX foci which mark the DSBs are stained, individual breaks are detectible, making the assay suitable for situations requiring great sensitivity. While the methods for the detection of γ-H2AX foci are still evolving, particularly for in vivo detection, the basic assay has proven to be useful in several diverse areas of research. We will highlight recent developments of the assay in four areas: radiation biodosimetry, the evaluation or validation of new cancer drugs in clinical studies, chronic inflammation, and environmental genotoxicity.
Highlights
The creation of a double-strand break (DSB) in eukaryotic cells is generally accompanied by the formation of hundreds of histone -H2AX (H2AXS139PO4 in humans) molecules in the chromatin flanking the double‐strand breaks (DSBs) site [1]
The foci serve as sites for accumulation of other proteins involved in DSB repair, leading to the suggestion that the foci have roles in signal amplification and the accumulation of DNA repair factors that, in turn, facilitate chromatin remodeling, cell cycle checkpoint functioning, sister chromatid-dependent recombinational repair and chromatin anchoring to prevent the dissociation of broken ends [reviewed in [1,2,3,4,5]]
If increased levels of foci and DSB damage in lymphocytes and adipose tissue is indicative of increased damage levels elsewhere, these findings provide a possible molecular mechanism by which obesity may lead to increased cancer risk
Summary
The creation of a double-strand break (DSB) in eukaryotic cells is generally accompanied by the formation of hundreds of histone -H2AX (H2AXS139PO4 in humans) molecules in the chromatin flanking the DSB site [1]. While studies reported the use of γ-H2AX foci induction following exposure to therapeutic doses of ionizing radiation [9,11,12,13,14,15], how the assay would perform at higher doses, in humans, remained unclear. The specificity of many cancer drugs for replicating cells creates a problem concerning appropriate tissues to sample for measuring -H2AX foci formation.
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