Expression of the Oxidative Base Excision Repair Enzymes is not Induced in TK6 Human Lymphoblastoid Cells after Low Doses of Ionizing Radiation

Inoue, Masaaki; Gp, Shen; Ma, Chaudhry; Galick, Heather; Jo, Blaisdell; Wallace, Susan S.

doi:10.1667/3163

Cited by 40 publications

(18 citation statements)

References 72 publications

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“…The low doses of ionizing radiation that institute the adaptive response, ie, enhanced resistance to subsequent radiation challenges, did not induce expression of BER enzymes or their messenger RNAs (mRNAs) in human lymphoblastoid cells (Inoue et al 2004). The mRNA and cellular BER protein levels were not elevated.…”

Section: Discussionmentioning

confidence: 97%

Clonogenicity of human leukemic cells protected from cell-lethal agents by heat shock protein 70

Bases

2005

Cell Stress Chaper

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Pretreatment of human leukemia THP-1 cells with heat shock protein Hsp70 (Hsp70) protected them from the cell-lethal effects of the topoisomerase II inhibitor, lucanthone and from ionizing radiation. Cell viability was scored in clonogenic assays of single cells grown in liquid medium containing 0.5% methyl cellulose. Colonies were observed and rapidly scored after staining with the tetrazolium salt, 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide. The frequency of abasic sites in the deoxyribonucleic acid (DNA) of THP-1 cells was reduced when these cells were treated with Hsp70. Hsp70 is presumed to have protected the cells by promoting repair of cell DNA, in agreement with previous studies that showed that Hsp70 enhanced base excision repair by purified enzymes. The shoulders of radiation dose-response curves were enhanced by pretreatment of cells with Hsp70 and, importantly, were reduced when cells were transfected with ribonucleic acid designed to silence Hsp70. Hsp70 influenced repair of sublethal damage after radiation.

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Section: Discussionmentioning

confidence: 97%

Clonogenicity of human leukemic cells protected from cell-lethal agents by heat shock protein 70

Bases

2005

Cell Stress Chaper

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“…Another study from our laboratory examined the effects of ionizing radiation in normal human cells and did not find upregulation of BER genes. 34 Endogenous DNA damage as a result of free radical production is repaired by BER. Due to continuous production of free radicals as a result of cellular metabolism, the BER machinery of the cell is expected to be active.…”

Section: Discussionmentioning

confidence: 99%

Radiation‐induced gene expression profile of human cells deficient in 8‐hydroxy‐2′‐deoxyguanine glycosylase

Chaudhry

2005

Intl Journal of Cancer

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The human OGG1 gene encodes a DNA glycosylase that is involved in the base excision repair of 8-hydroxy-2 0 -deoxyguanine (8-OH-dG) from oxidatively damaged DNA. Cellular 8-OH-dG levels accumulate in the absence of this activity and could be deleterious for the cell. To assess the role of 8-oxoguanine glycosylase (OGG1) in the cellular defense mechanism in a specific DNA repair defect background, we set out to determine the expression pattern of base excision repair genes and other cellular genes not involved in the base excision pathway in OGG1-deficient human KG-1 cells after ionizing radiation exposure. KG-1 cells have lost OGG1 activity due to a homozygous mutation of Arg229Gln. Gene expression alterations were monitored at 4, 8, 12 and 24 hr in 2 Gy irradiated cells. Large-scale gene expression profiling was assessed with DNA microarray technology. Gene expression analysis identified a number of ionizing radiation-responsive genes, including several novel genes. There were 2 peaks of radiationinduced gene induction or repression: one at 8 hr and the other at 24 hr. Overall the number of downregulated genes was higher than the number of upregulated genes. The highest number of downregulated genes was at 8 hr postirradiation. Genes corresponding to cellular, physiologic, developmental and extracellular processes were identified. The highest number of radiationinduced genes belonged to the signal transduction category, followed by genes involved in transcription and response to stress. Microarray gene expression data were independently validated by relative quantitative RT-PCR. Surprisingly, none of the genes involved in the base excision repair of radiation-induced DNA damage showed altered expression. ' 2005 Wiley-Liss, Inc.

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“…The analysis was performed as described by Inoue et al [2004], with T cells exposed to 137 Cs radiation. RNA was extracted from 4 Â 10 6 cells/sample and checked by agarose gel electrophoresis and spectropho- tometry.…”

Section: Real-time Quantitative Rt-pcrmentioning

confidence: 99%

“…Other studies have shown the induction of ionizing irradiation-responsive genes in peripheral blood T lymphocytes by cDNA microarray hybridization, suggesting that the levels of gene expression may provide another estimate of radiation exposure [Amundson et al, 2000;Amundson and Fornace, 2003]. We then studied the possible induction of the CDKN1A/WAF1 gene (the cyclin-dependent kinase inhibitor, p21) because it was shown to be strongly induced by exposure to 200 cGy irradiation in both human peripheral blood T cells and lymphoblastoid cells [Amundson et al, 2000;Inoue et al, 2004]. As shown in Figure 3, there was no significant induction of WAF1 by 4 hr after irradiation with up to 200 cGy, the time period during which the genetic damage occurs.…”

Section: Cytotoxicity and Mutagenicity Of 137 Cs Irradiationmentioning

confidence: 99%

In vitro studies of the genotoxicity of ionizing radiation in human G0 T lymphocytes

O’Neill

Nicklas

Hirsch

et al. 2005

Environ. Mol. Mutagen.

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In an effort to mimic human in vivo exposures to ionizing irradiation, G(0) phase T lymphocytes from human peripheral blood samples were utilized for in vitro studies of the genotoxic effects of (137)Cs low-LET irradiation and (222)Rn high-LET irradiation. Both types of radiation induced mutations in the HPRT gene in a dose-dependent manner, with a mutant frequency (MF) = 4.28 + 1.34x + 7.51x(2) for (137)Cs (R(2) = 0.95) and MF = 4.81 + 0.67x for (222)Rn (R(2) = 0.51). Post (137)Cs irradiation incubation in the presence of cytosine arabinoside, a reversible inhibitor of DNA repair, caused an increase in the MF over irradiation alone, consistent with a misrepair mechanism being involved in the mutagenicity of low-LET irradiation. The spectrum of (137)Cs irradiation-induced mutation displayed an increase in macro-deletions (in particular total gene deletions) and rearrangement events, some of which were further defined by either chromosome painting or direct DNA sequencing. The spectrum of (222)Rn irradiation-induced mutation was characterized by an increase in small alterations, especially multiple single base deletions/substitutions and micro-deletions. These studies define the specific response of human peripheral blood T cells to ionizing irradiation in vitro and form a basis for evaluating the genotoxic effects of human in vivo exposure.

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Expression of the Oxidative Base Excision Repair Enzymes is not Induced in TK6 Human Lymphoblastoid Cells after Low Doses of Ionizing Radiation

Cited by 40 publications

References 72 publications

Clonogenicity of human leukemic cells protected from cell-lethal agents by heat shock protein 70

Clonogenicity of human leukemic cells protected from cell-lethal agents by heat shock protein 70

Radiation‐induced gene expression profile of human cells deficient in 8‐hydroxy‐2′‐deoxyguanine glycosylase

In vitro studies of the genotoxicity of ionizing radiation in human G0 T lymphocytes

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