| Human embryonic stem cells may display higher resistance to genotoxic stress as compared to primary explanted somatic cells. | |
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MedLine Citation:
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PMID: 18498216 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The use of human embryonic stem (hES) cells in genotoxicity screening can potentially overcome the deficiencies associated with using immortalized cell lines, primary explanted somatic cells, and live animal models. Hence this study sought to compare the responses of hES cells and primary explanted somatic cells (IMR-90 cells, human fetal lung fibroblasts) to genotoxic stress, to evaluate whether hES cells can accurately reflect the normal physiology of human somatic cells. The effects of mitomycin C (MMC) on the chromosomal stability of hESC and IMR-90 was assayed and compared by fluorescence in situ hybridization (FISH) with telomere-specific peptide nucleic acid and multicolor (m) FISH techniques. The results showed that, the percentage of aberrant cells increased from 6% in the untreated control to 57.5% at the higher dose of 0.06 microg/ml MMC (9.6-fold increase) group in the case of IMR-90 cells, whereas hES cells displayed a corresponding increase from 6% to 28% (4.6-fold increase). Telomere FISH ascertained that the main types of damage induced by MMC are chromosomal breaks and the loss of telomeric signals. No fusions were observed in all samples analyzed. This was further confirmed by mFISH, which showed that fusions and translocations were not the type of aberration induced by MMC, with no such aberrations being observed in all samples analyzed. Hence, hES cells of the H1 line are apparently more resistant to MMC-induced DNA damage, as compared to the IMR-90 cells. These results highlight possible intrinsic differences in response to damaging agents between hES cells and normal somatic cells. |
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Authors:
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Kumar Jayaseelan Vinoth; Boon Chin Heng; Anuradha Poonepalli; Birendranath Banerjee; Lakshmidevi Balakrishnan; Kai Lu; M Prakash Hande; Tong Cao |
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Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: Stem cells and development Volume: 17 ISSN: 1547-3287 ISO Abbreviation: Stem Cells Dev. Publication Date: 2008 Jun |
Date Detail:
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Created Date: 2008-06-25 Completed Date: 2008-08-29 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101197107 Medline TA: Stem Cells Dev Country: United States |
Other Details:
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Languages: eng Pagination: 599-607 Citation Subset: IM |
Affiliation:
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Stem Cell Program, Faculty of Dentistry, National University of Singapore, 119074 Singapore. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cells, Cultured Chromosome Breakage / drug effects DNA Damage* / drug effects Drug Resistance* / drug effects Embryonic Stem Cells / metabolism* Fibroblasts / drug effects, metabolism* Humans In Situ Hybridization, Fluorescence Karyotyping Metaphase / drug effects Mice Mitomycin / pharmacology Peptide Nucleic Acids / metabolism Telomere / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Peptide Nucleic Acids; 50-07-7/Mitomycin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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