Unknown,Transcriptomics,Genomics,Proteomics

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Gene expression profile of bone marrow with post-irradiation radioprotector

ABSTRACT: To elucidate the mechanism of the in vivo radioprotection activity of Zn-containing heat-treated Saccharomyces cerevisiae yeast (Zn-yeast), expression changes in bone marrow after whole body irradiation (WBI) with concomitant treatment of Zn-yeast were analyzed using microarray technology. Keywords: mouse, bone marrow, Zn-containing heat-treated yeast administration, gamma-irradiation Zn-yeast suspension was administered i.p. into C3H mice immediately after 7.5 Gy WBI. Bone marrow from irradiated mice was extracted at 6 hours after irradiation and analyzed by microarray containing of 44,000 probes.

ORGANISM(S): Mus musculus

SUBMITTER: Kaori Imadome

PROVIDER: E-GEOD-18727 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Vascular homeostasis regulators, Edn1 and Agpt2, are upregulated as a protective effect of heat-treated zinc yeast in irradiated murine bone marrow.

Ueno Megumi M Imadome Kaori K Iwakawa Mayumi M Anzai Kazunori K Ikota Nobuo N Imai Takashi T

Journal of radiation research 20100101 5

<h4>Purpose</h4>To elucidate the mechanism underlying the in vivo radioprotection activity by Zn-containing, heat-treated Saccharomyces cerevisiae yeast (Zn-yeast).<h4>Materials and methods</h4>Zn-yeast suspension was administered into C3H/He mice immediately after whole body irradiation (WBI) at 7.5 Gy. Bone marrow was extracted from the mice 6 hours after irradiation and analyzed on a microarray. Expression changes in the candidate responsive genes differentially expressed in treated mice were ...[more]

PMID: 20921820

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Project description:Measuring global gene expression using cDNA or oligonucleotide microarrays is an effective approach to understanding the complex mechanisms of the effects of radiation. However, few studies have been carried out that investigate gene expression in vivo after prolonged exposure to low-dose-rate radiation. In this study, C57BL/6J mice were continuously irradiated with ?-rays for 485 days at dose-rates of 0.032 – 13 ?Gy/min. Gene expression profiles in the kidney and testis from irradiated and unirradiated mice were analyzed, and differentially expressed genes were identified. A combination of pathway analysis and hierarchical clustering of differentially expressed genes revealed that expression of genes involved in mitochondrial oxidative phosphorylation was elevated in the kidney after irradiation at the dose-rates of 0.65 ?Gy/min and 13 ?Gy/min. Expression of cell cycle-associated genes was not profoundly modulated in the kidney, in contrast to the response to acute irradiation, suggesting a threshold in the dose-rate for modulation of the expression of cell cycle-related genes in vivo following exposure to radiation. We demonstrated that changes to the gene expression profile in the testis were largely different from those in the kidney. The Gene Ontology categories “DNA metabolism”, “response to DNA damage” and “DNA replication” overlapped significantly with the clusters of genes whose expression decreased with an increase in the dose-rate to the testis. These observations provide a fundamental insight into the organ-specific responses to low-dose-rate radiation. Key Words: kidney, low-dose-rate, radiation, microarray, mitochondrial oxidative phosphorylation, testis 3 biological replicates for each experimental group were analysed. GSE14290_Kidney_raw_data.csv contains the raw data for GSM357146, GSM357425, GSM357426, GSM357452 to GSM357460. GSE14290_Testis_raw_data.csv contains the raw data for GSM357471 to GSM357482. In these files, the sample identifiers are included in the column headers.

Project description:Children are considered more sensitive to radiation-induced cancer than adults, yet any differences in genomic alterations associated with age at exposure and their underlying mechanisms remain unclear. We analyzed the mutation of key tumor suppressor genes in T-cell lymphomas arising after weekly irradiation of female B6C3F1 mice with 1.2 Gy X-rays for 4 consecutive weeks starting during infancy (1 week old), adolescence (4 weeks old) or as young adults (8 weeks old). T-cell lymphoma incidence did not show any statistical differences among three irradiated groups; however, the frequency of loss of heterozygosity on chromosomes 11 and 19 showed opposing correlations with age at exposure. Ikaros on chromosome 11 was mutated frequently in the young adultâ??irradiation group (63%; 5/8), frequently incurring multiple independent hits (including deletions and mutations) or suffering a single hit predicted to result in a dominant negative protein (such as those lacking exon 4, an isoform we have designated Ik11, which lacks two of the four zincâ??finger domains important for DNA binding). Pten on chromosome 19 was mutated more frequently in tumors from infant- (67%; 10/15) compared with young adult-irradiated mice (13%; 1/8, P = 0.041). Despite the presence of homozygous Pten mutations, DNA copy number was unchanged in the infant-irradiation group, suggesting duplication of the mutated allele by chromosome mis-segregation or mitotic recombination. Taken together, our findings demonstrate that while deletions on chromosome 11 affecting the Ikaros locus are a prominent feature of young adult irradiation-induced T-cell lymphoma, tumors arising after infant irradiation suffer a second hit in the Pten gene by chromosome mis-segregation or recombination. This is the first report showing age-at-exposure associated radiation-induced genomic alterations in two key tumor suppressor genes linked to T-cell lymphomagenesis. These data are important for considering the risks associated with childhood exposure to radiation. 38 T-cell lymphomas arising after weekly irradiation of female B6C3F1 mice with 1.2 Gy X-rays for 4 consecutive weeks starting at different ages (Infant: 1 week old (15 tumors), Adolescent: 4 weeks old (13 tumors), Young adult: 8 weeks old (10 tumors)) were analyzed.

Dataset Information

Gene expression profile of bone marrow with post-irradiation radioprotector

Publications

Vascular homeostasis regulators, Edn1 and Agpt2, are upregulated as a protective effect of heat-treated zinc yeast in irradiated murine bone marrow.

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