Genetic Variation in Radiation-Induced Expression Phenotypes

Correa, Candace R.; Cheung, Vivian G.

doi:10.1086/425221

Cited by 56 publications

(39 citation statements)

References 15 publications

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“…The reduction in micronuclei frequency was varied in different donors. These results were consistent with previous findings that radioadaptive response varied among different individuals/cell lines (Correa and Cheung;2004;Jiang et al 2008).…”

Section: Discussionsupporting

confidence: 93%

Modification in the Expression of MRE11/RAD50/NBS1 Complex in Low dose Irradiated Human Lymphocytes

Singh¹,

Bala

Kumar

et al. 2009

Dose-Response

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Despite the fact that high doses of radiation are detrimental, low dose radiation (LDR) often protects the organism against a subsequent exposure of lethal doses of radiation. Present study was undertaken to understand the role of Mre11, Rad50 and Nbs1 genes in the low dose radio-adapted human peripheral blood mononuclear cells (PBMCs). Optimum time interval between low dose (0.07 Gy) and high dose (5.0 Gy) of 60Co-γ-radiation was observed to be 5.0 hours, at which PBMCs showed maximum LDR induced resistance (RIR). At cytogenetic level, micronuclei frequency was found to be reduced in LDR pre-irradiated PBMCs subsequently exposed to high dose radiation (HDR) as compared to controls. At transcriptional level, with reference to sham-irradiated cells significantly (p≤0.05) altered expression of Mre11, Rad50 and Nbs1 genes was observed in low dose irradiated cells. At protein level, Mre11, Rad50 and Nbs1 were enhanced significantly (p≤0.05) in low dose pre-irradiated cells subsequently exposed to high dose of radiation as compared to only high dose irradiated cells. Transcriptional as well as translational modulation in the expression of MRN complex components upon low dose irradiation may confer its participation in repair pathways, resulting in induced resistance.

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Section: Discussionsupporting

confidence: 93%

Modification in the Expression of MRE11/RAD50/NBS1 Complex in Low dose Irradiated Human Lymphocytes

Singh¹,

Bala

Kumar

et al. 2009

Dose-Response

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show abstract

“…Cultures of each cell type (lymphoblast and fibroblast) and genetic background [wild type (WT) and AT] were analyzed from multiple individuals to gain information about the ATMdependent and ATM-independent responses while reducing the effects of individual genetic variation (11,12). Initially, six lymphoblast cultures (three WT and three AT) and six fibroblast cultures (three WT and three AT) were exposed to 5 Gy IR (10) for a comparison of IR treatment between cell types.…”

Section: Resultsmentioning

confidence: 99%

ATM Requirement in Gene Expression Responses to Ionizing Radiation in Human Lymphoblasts and Fibroblasts

Innes¹,

Heinloth

Flores³

et al. 2006

Molecular Cancer Research

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The heritable disorder ataxia telangiectasia (AT) is caused by mutations in the AT-mutated (ATM) gene with manifestations that include predisposition to lymphoproliferative cancers and hypersensitivity to ionizing radiation (IR). We investigated gene expression changes in response to IR in human lymphoblasts and fibroblasts from seven normal and seven AT-affected individuals. Both cell types displayed ATM-dependent gene expression changes after IR, with some responses shared and some responses varying with cell type and dose. Interestingly, after 5 Gy IR, lymphoblasts displayed ATM-independent responses not seen in the fibroblasts at this dose, which likely reflect signaling through ATM-related kinases, e.g., ATR, in the absence

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“…Because cellular responses rely in part on changes in gene expression, the extent to which the radiation-responsive genes are induced or repressed influences how cells deal with radiation exposure, where individual variability of radiation sensitivity is observed at the gene expression level (10,11). In 2000, lehnert et al reported that gene chips could be used to survey radiation-associated genes (12).…”

Section: Introductionmentioning

confidence: 99%

CDC25A, VAV1, TP73, BRCA1 and ZAP70 gene overexpression correlates with radiation response in colorectal cancer

Tok

2011

Oncol Rep

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Abstract. radiotherapy is increasingly used in adjuvant approaches for colorectal cancer (crc) to reduce local recurrence and improve survival. However, the principal limitation is the large variability in response among different individuals due to tumor heterogeneity. In the present study, we compared gene expression profiles between radiosensitive and radioresistant colorectal cancer cell lines to identify radiation-related molecules that can be used to evaluate the effects of radiation. the crc cell line sW620 was irradiated with a high-energy photo beam. Following radiation treatment, rnA was extracted from non-irradiated and irradiated cells, respectively, and gene expression analysis was performed by oligonucleotide microarray and the DAVID bioinformatics method. to further confirm the results, an additional 4 crc cell lines, colo205, t84, Hct116, sW480 and sW403 were purchased from Atcc. the radiosensitivities of each were determined by the survival fraction at 2 gray (sF2) of the surviving cells using the Atplite assay, and the gene expression profiles after irradiation among the radiosensitive and radioresistant cell lines were analyzed by membrane arrays. the relationships between gene expression and patient clinicopathological features were also analyzed using membrane arrays and rt-pcr. the results from oligonucleotide microarray analysis show that 1601 genes were up-regulated (gene expression ratio of post-to preradiation treatment >2). By bioinformatic database analysis, 30 up-regulated genes were identified as involved in DNA damage response pathways, immune response pathways and the complement and coagulation cascades pathway. Fifteen genes showed differential gene expression profiles between radiosensitive (Hct116 and sW620) and radioresistant crc cell lines (sW403 and sW480). In 110 crc tissues, we detected five genes CDC25A, VAV1, TP73, BRCA1 and ZAP70 from 15 overexpressed genes that significantly related to prognostic factors (tumor size, advanced stage, invasive depth, lymph node metastasis and differentiation). these findings suggest that cDc25A, VAV1, tp73, BrcA1 and ZAp70 may be novel markers for predicting the effectiveness of radiotherapy in crc patients.

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Genetic Variation in Radiation-Induced Expression Phenotypes

Cited by 56 publications

References 15 publications

Modification in the Expression of MRE11/RAD50/NBS1 Complex in Low dose Irradiated Human Lymphocytes

Modification in the Expression of MRE11/RAD50/NBS1 Complex in Low dose Irradiated Human Lymphocytes

ATM Requirement in Gene Expression Responses to Ionizing Radiation in Human Lymphoblasts and Fibroblasts

CDC25A, VAV1, TP73, BRCA1 and ZAP70 gene overexpression correlates with radiation response in colorectal cancer

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