Identification of differentially transcribed genes in human lymphoblastoid cells irradiated with 0.5 Gy of γ-ray and the involvement of low dose radiation inducible<i>CHD6</i>gene in cell proliferation and radiosensitivity

Wang, H P; Long, Xiaodong; Sun, Zhaoyun; Rigaud, O.; Xu, Qin; Huang, Yu Chen; Jianli, Sui; Bai, Bei; Zhou, Ping

doi:10.1080/09553000600632261

Cited by 34 publications

(27 citation statements)

References 26 publications

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“…Although this is the first report that provides evidence for the role of a CHD family member in DNA repair, an earlier study has shown the induction of CHD6 in response to low dose gamma-ray irradiation in various cell lines. Interestingly, silencing of CHD6 also increased the resistance of A549 cells to low dose radiation, whereas radiosensitivity was unchanged in response to doses larger than 4 Gy, implicating a mechanistic role of CHD6 in cellular responses to low dose radiation [Wang et al, 2006]. In addition, the CHD4 protein has been shown to interact with the ataxia telangiectasia mutated and Rad3-related protein (ATR) that is known to be involved in various DNA damage response pathways [Schmidt and Schreiber, 1999;Abraham, 2001;Durocher and Jackson, 2001].…”

Section: Discussionmentioning

confidence: 97%

Chromodomain helicase DNA‐binding protein 2 affects the repair of X‐ray and UV‐Induced DNA damage

Rajagopalan

Nepa

Venkatachalam

2011

Environ and Mol Mutagen

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Eukaryotic cells have evolved a variety of parallel and redundant DNA damage response pathways that function in a coordinated fashion to prevent the fixation of DNA damage as mutations. Despite the wealth of knowledge on DNA damage signaling on downstream cellular events, the mechanisms of DNA damage recognition, DNA repair as well as DNA damage signaling in the context of chromatin is poorly understood. Chromodomain helicase DNA-binding proteins (CHD) belong to a group of highly conserved chromatin remodeling proteins that are implicated in regulation of transcription. In an effort to understand the physiological role of one of the CHD members in a mammalian model system, we developed a mutant mouse model for the Chd2 gene. The Chd2 mutant mice are highly susceptible to spontaneous lymphoid tumor formation. In this study, we present evidence that the Chd2 mutant cells are defective in their ability to repair DNA damage induced by ionizing and ultraviolet radiation. Consistent with the role of Chd2 in regulating DNA damage responses, the Chd2 mutant cells are also sensitive to DNA damaging agents in clonogenic assays. In summary, our data suggest that the Chd2 protein is involved in regulating the DNA damage responses at the chromatin level.

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Section: Discussionmentioning

confidence: 97%

Chromodomain helicase DNA‐binding protein 2 affects the repair of X‐ray and UV‐Induced DNA damage

Rajagopalan

Nepa

Venkatachalam

2011

Environ and Mol Mutagen

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“…There is an increasing concern about the hazardous effects caused by a 'very-low' (<0.2 Gy) dose of IR. While there are several large-scale gene expression studies for the differential effect between the high (>2 Gy) and low (<2 Gy) dose of IR (24)(25)(26)(27), there are fewer studies concerning the low and 'very-low' dose effects on gene expression. Moreover, most of the low or 'very-low' dose-based IR studies were performed at a single fixed time point following exposure without any consideration of the time-dependent experimental effects.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of time- and dose-dependent patterns of gene expression in a human mesenchymal stem cell line exposed to low-dose ionizing radiation

Jin¹,

Na²,

Lee³

et al. 2008

Oncol Rep

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Abstract.We focused on the transcriptional responses induced by low and very low doses of ionizing radiation with time effect. Regardless of their importance only a few limited studies have been done. Here we applied a large-scale gene transcript profile to elucidate the genes and biological pathways. Immortalized human mesenchymal stem cells were irradiated with 0.01, 0.05, 0.2 and 1 Gy of gamma radiation and total RNA was extracted from each cell line at 1, 4, 12 and 48 h after exposure. The essential transcriptional responses were identified according to dose and time. A total of 6,016 genes showed altered expression patterns at more than one time point or dose level among the investigated 10,800 genes. Genes that showed dose-dependent expression responses were involved in signal transduction, regulation of transcription, proteolysis, peptidolysis and metabolism. Those that showed time-dependent responses were divided into two distinct groups: the up-and-down group was associated with 'cellular defense mechanisms' such as apoptosis, cell adhesion, stress response and immune response and the down-and-up group with 'fundamental cellular processes' such as DNA replication, mitosis, RNA splicing, DNA repair and translation initiation. Genes showing both dose-and time-dependent responses exhibited a mixture of both features. A highly non-linear relationship between the IR dose and the transcriptional relative response was obtained from the dose-dependent group. The timedependent group also exhibited a non-linear relationship as the complex effect group did. Some of the early-reactive-phase (1-4 h) genes showed a differential expression response to 0.01, 0.05 and 0.2 Gy but were unresponsive to 1 Gy. Some of the late-recovery-phase (12-48 h) genes showed a differential expression to 1 Gy but were relatively unresponsive to other doses. We further characterized the gene expression patterns that could be implicated in the molecular mechanism of the cellular responses to low and very low-dose irradiation.

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“…We focused our study on 24 radiation responsive ERP29 ERP29 candidate genes because these genes were previously documented to be connected with functions intimately linked to cancer (Table 2). [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] Among the 24 genes, observations from previous studies noted post CT changes within 1 hour after radiation in 11 genes with 4 of them (ATM, ERP29, TP53, CDKN2A) showing post CT changes from very low radiation doses, as low as 0.1 Gy. Owing to their higher radiosensitivity, children are expected to react more sensitively than adults to the CT-induced radiation insult, and therefore, we included all 24 genes in our study, although some observations were reported longer than 1 hr post CT or after IR doses higher than those used in our study.…”

Section: Discussionmentioning

confidence: 99%

Changes in Whole Blood Gene Expression after Computed Tomography in Children: A Pilot Study

Halm

Tiirikainen²,

Lai³

et al. 2015

Gene Expression to Genetical Genomics

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ABSTRACT:Computed tomography (CT) exposes patients to ionizing X-irradiation (IR) that can alter the expression of genes responsible for controlling complex regulatory pathways. We sought to determine trends in the expression of 24 documented radiation-responsive genes linked to cancer in vivo. A total of 17 children (0.25-6 years old) undergoing medically indicated CT examinations with radiation doses ranging from 92.46 to 525.55 mGy cm (equivalent to effective doses of 0.78-11.30 mSv) were enrolled. Blood was drawn immediately before and 1 hour after their CT exams and mixed with an RNA additive for stabilization of gene expression. RNA samples of 14 of the 17 children were analyzed on a gene expression microarray. Absolute changes in gene expression were subtle, averaging less than 10%, but trends in expression changes of several genes were observed. ERP29, an endoplasmic reticulum chaperone, thought to be involved in the folding of secretory proteins, showed significant change in expression (8% decrease, P = 0.002) in the expected direction consistent with previous literature. PCNA expression increased linearly with CT dose (mGy cm) (P = 0.001). TP53 and FLT3LG expression increased linearly with effective dose (mSv) (P = 0.02 and P = 0.02). Previous IR exposure was associated with decreased GADD45A (P = 0.001) and FLT3LG (P = 0.03) and increased MDM2 expression (P = 0.02). We observed in this pilot study modest gene expression changes in the 24 IR-responsive candidate genes studied. Our results showed trends in gene expression changes, and they need to be confirmed in future studies with larger sample sizes to help develop risk assessments and preventive modalities for young patients undergoing CT.

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Identification of differentially transcribed genes in human lymphoblastoid cells irradiated with 0.5 Gy of γ-ray and the involvement of low dose radiation inducibleCHD6gene in cell proliferation and radiosensitivity

Abstract: This study has identified a set of genes responsive to 0.5 Gy of gamma-rays. CDH6 gene can be specifically up-regulated by low dose irradiation, and its inducible expression could be involved in a low dose hypersensitive response.

Cited by 34 publications

References 26 publications

Chromodomain helicase DNA‐binding protein 2 affects the repair of X‐ray and UV‐Induced DNA damage

Chromodomain helicase DNA‐binding protein 2 affects the repair of X‐ray and UV‐Induced DNA damage

Comprehensive analysis of time- and dose-dependent patterns of gene expression in a human mesenchymal stem cell line exposed to low-dose ionizing radiation

Changes in Whole Blood Gene Expression after Computed Tomography in Children: A Pilot Study

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