| DNA damage signaling assessed in individual cells in relation to the cell cycle phase and induction of apoptosis. | |
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MedLine Citation:
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PMID: 23137030 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Reviewed are the phosphorylation events reporting activation of protein kinases and the key substrates critical for the DNA damage signaling (DDS). These DDS events are detected immunocytochemically using phospho-specific Abs; flow cytometry or image-assisted cytometry provide the means to quantitatively assess them on a cell by cell basis. The multiparameter analysis of the data is used to correlate these events with each other and relate to the cell cycle phase, DNA replication and induction of apoptosis. Expression of γH2AX as a possible marker of induction of DNA double strand breaks is the most widely studied event of DDS. Reviewed are applications of this multiparameter approach to investigate constitutive DDS reporting DNA damage by endogenous oxidants byproducts of oxidative phosphorylation. Also reviewed are its applications to detect and explore mechanisms of DDS induced by variety of exogenous agents targeting DNA such as exogenous oxidants, ionizing radiation, radiomimetic drugs, UV light, DNA topoisomerase I and II inhibitors, DNA crosslinking drugs and variety of environmental genotoxins. Analysis of DDS induced by these agents provides often a wealth of information about mechanism of induction and the type of DNA damage (lesion) and is reviewed in the context of cell cycle phase specificity, DNA replication, and induction of apoptosis or cell senescence. Critically assessed is interpretation of the data as to whether the observed DDS events report induction of a particular type of DNA lesion. |
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Authors:
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Zbigniew Darzynkiewicz; Hong Zhao; H Dorota Halicka; Paulina Rybak; Jurek Dobrucki; Donald Wlodkowic |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-11-9 |
Journal Detail:
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Title: Critical reviews in clinical laboratory sciences Volume: - ISSN: 1549-781X ISO Abbreviation: Crit Rev Clin Lab Sci Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8914816 Medline TA: Crit Rev Clin Lab Sci Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Brander Cancer Research Institute and Department of Pathology, New York Medical College , Valhalla, NY , USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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