Profiles of global gene expression in ionizing-radiation--damaged human diploid fibroblasts reveal synchronization behind the G1 checkpoint in a G0-like state of quiescence.
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| Title: | Profiles of global gene expression in ionizing-radiation--damaged human diploid fibroblasts reveal synchronization behind the G1 checkpoint in a G0-like state of quiescence. |
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| Authors: | Zhou T (AUTHOR), Chou JW (AUTHOR), Simpson DA (AUTHOR), Zhou Y (AUTHOR), Mullen TE (AUTHOR), Medeiros M (AUTHOR), Bushel PR (AUTHOR), Paules RS (AUTHOR), Yang X (AUTHOR), Hurban P (AUTHOR), Lobenhofer EK (AUTHOR), Kaufmann WK (AUTHOR) |
| Source: | Environmental Health Perspectives. Apr2006, Vol. 114 Issue 4, p553-559. 7p. |
| Abstract: | Cell cycle arrest and stereotypic transcriptional responses to DNA damage induced by ionizing radiation (IR) were quantified in telomerase-expressing human diploid fibroblasts. Analysis of cytotoxicity demonstrated that 1.5 Gy IR inactivated colony formation by 40-45% in three fibroblast lines; this dose was used in all subsequent analyses. Fibroblasts exhibited > 90% arrest of progression from G2 to M at 2 hr post-IR and a similarly severe arrest of progression from G1 to S at 6 and 12 hr post-IR. Normal rates of DNA synthesis and mitosis 6 and 12 hr post-IR caused the S and M compartments to empty by > 70% at 24 hr. Global gene expression was analyzed in IR-treated cells. A microarray analysis algorithm, EPIG, identified nine IR-responsive patterns of gene expression that were common to the three fibroblast lines, including a dominant p53-dependent G1 checkpoint response. Many p53 target genes, such as CDKN1A, GADD45, BTG2, and PLK3, were significantly up-regulated at 2 hr post-IR. Many genes whose expression is regulated by E2F family transcription factors, including CDK2, CCNE1, CDC6, CDC2, MCM2, were significantly down-regulated at 24 hr post-IR. Numerous genes that participate in DNA metabolism were also markedly repressed in arrested fibroblasts apparently as a result of cell synchronization behind the G1 checkpoint. However, cluster and principal component analyses of gene expression revealed a profile 24 hr post-IR with similarity to that of G0 growth quiescence. The results reveal a highly stereotypic pattern of response to IR in human diploid fibroblasts that reflects primarily synchronization behind the G1 checkpoint but with prominent induction of additional markers of G0 quiescence such as GAS1. [ABSTRACT FROM AUTHOR] |
| Copyright of Environmental Health Perspectives is the property of National Institute of Environmental Health Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| URL: | 20814554 |
| Database: | GreenFILE |
| FullText | Links: – Type: pdflink Text: Availability: 0 |
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| Header | DbId: 8gh DbLabel: GreenFILE An: 106148355 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Profiles of global gene expression in ionizing-radiation--damaged human diploid fibroblasts reveal synchronization behind the G1 checkpoint in a G0-like state of quiescence. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Zhou+T%22">Zhou T</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Chou+JW%22">Chou JW</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Simpson+DA%22">Simpson DA</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zhou+Y%22">Zhou Y</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Mullen+TE%22">Mullen TE</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Medeiros+M%22">Medeiros M</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bushel+PR%22">Bushel PR</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Paules+RS%22">Paules RS</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Yang+X%22">Yang X</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Hurban+P%22">Hurban P</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Lobenhofer+EK%22">Lobenhofer EK</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Kaufmann+WK%22">Kaufmann WK</searchLink> (AUTHOR) – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Environmental+Health+Perspectives%22">Environmental Health Perspectives</searchLink>. Apr2006, Vol. 114 Issue 4, p553-559. 7p. – Name: Abstract Label: Abstract Group: Ab Data: Cell cycle arrest and stereotypic transcriptional responses to DNA damage induced by ionizing radiation (IR) were quantified in telomerase-expressing human diploid fibroblasts. Analysis of cytotoxicity demonstrated that 1.5 Gy IR inactivated colony formation by 40-45% in three fibroblast lines; this dose was used in all subsequent analyses. Fibroblasts exhibited > 90% arrest of progression from G2 to M at 2 hr post-IR and a similarly severe arrest of progression from G1 to S at 6 and 12 hr post-IR. Normal rates of DNA synthesis and mitosis 6 and 12 hr post-IR caused the S and M compartments to empty by > 70% at 24 hr. Global gene expression was analyzed in IR-treated cells. A microarray analysis algorithm, EPIG, identified nine IR-responsive patterns of gene expression that were common to the three fibroblast lines, including a dominant p53-dependent G1 checkpoint response. Many p53 target genes, such as CDKN1A, GADD45, BTG2, and PLK3, were significantly up-regulated at 2 hr post-IR. Many genes whose expression is regulated by E2F family transcription factors, including CDK2, CCNE1, CDC6, CDC2, MCM2, were significantly down-regulated at 24 hr post-IR. Numerous genes that participate in DNA metabolism were also markedly repressed in arrested fibroblasts apparently as a result of cell synchronization behind the G1 checkpoint. However, cluster and principal component analyses of gene expression revealed a profile 24 hr post-IR with similarity to that of G0 growth quiescence. The results reveal a highly stereotypic pattern of response to IR in human diploid fibroblasts that reflects primarily synchronization behind the G1 checkpoint but with prominent induction of additional markers of G0 quiescence such as GAS1. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Environmental Health Perspectives is the property of National Institute of Environmental Health Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) – Name: URL Label: URL Group: URL Data: <link linkTarget="URL" linkTerm="20814554" linkWindow="_blank">20814554</link> |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1289/ehp.8026 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 7 StartPage: 553 Titles: – TitleFull: Profiles of global gene expression in ionizing-radiation--damaged human diploid fibroblasts reveal synchronization behind the G1 checkpoint in a G0-like state of quiescence. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Zhou T – PersonEntity: Name: NameFull: Chou JW – PersonEntity: Name: NameFull: Simpson DA – PersonEntity: Name: NameFull: Zhou Y – PersonEntity: Name: NameFull: Mullen TE – PersonEntity: Name: NameFull: Medeiros M – PersonEntity: Name: NameFull: Bushel PR – PersonEntity: Name: NameFull: Paules RS – PersonEntity: Name: NameFull: Yang X – PersonEntity: Name: NameFull: Hurban P – PersonEntity: Name: NameFull: Lobenhofer EK – PersonEntity: Name: NameFull: Kaufmann WK IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 04 Text: Apr2006 Type: published Y: 2006 Identifiers: – Type: issn-print Value: 00916765 Numbering: – Type: volume Value: 114 – Type: issue Value: 4 Titles: – TitleFull: Environmental Health Perspectives Type: main |
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