Prediction of Epigenetic and Stochastic Gene Expression Profiles of Late Effects after Radiation Exposure

Hirabayashi, Yoko; Inoue, Tohru

doi:10.1002/9781118349045.ch25

Cited by 6 publications

(12 citation statements)

References 30 publications

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“…The expression of key cell cycle regulation and checkpoint genes Ak1, Ccna1, Cdkn1a, Cdkn1b, Cdkn2a, Hus1, Npm2, Prmp1, Pmp22 and Trp63 were increased in response to total body irradiation [ 6 ]. Subsequent microarray analyses from other investigators indicated that up to 1302 genes were differentially expressed between 3–21 days postirradiation, affecting multiple biological processes including self-renewal, hematopoiesis, adhesion, differentiation, and immune response [ 8 , 9 , 10 ]. Additionally, ATM/CHEK2/p53 and AKT/PI3K signaling pathways were shown to be activated for as long as 4 weeks postirradiation, correlating with prolonged pro-apoptotic signaling following radiation exposure [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…Subsequent microarray analyses from other investigators indicated that up to 1302 genes were differentially expressed between 3–21 days postirradiation, affecting multiple biological processes including self-renewal, hematopoiesis, adhesion, differentiation, and immune response [ 8 , 9 , 10 ]. Additionally, ATM/CHEK2/p53 and AKT/PI3K signaling pathways were shown to be activated for as long as 4 weeks postirradiation, correlating with prolonged pro-apoptotic signaling following radiation exposure [ 8 , 9 ]. Experiments using qRT-PCR directed toward the detection of specific gene products associated with programmed cell death demonstrated increased expression of Bax and caspase-9 in total bone marrow cells following radiation exposure [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Bone Marrow Protein Oxidation in Response to Ionizing Radiation in C57BL/6J Mice

et al. 2014

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The bone marrow is one of the most radio-sensitive tissues. Accidental ionizing radiation exposure can damage mature blood cells and hematopoietic progenitor/stem cells, and mortality can result from hematopoietic insufficiency and infection. Ionizing radiation induces alterations in gene and protein expression in hematopoietic tissue. Here we investigated radiation effects on protein carbonylation, a primary marker for protein oxidative damage. C57BL/6 mice were either sham irradiated or exposed to 7.5 Gy 60Co (0.6 Gy/min) total body irradiation. Bone marrow was obtained 24 h post-irradiation. Two dimensional (2-D) gel electrophoresis and Oxyblot immunodetection were used to discover carbonylated proteins, and peptide mass fingerprinting was performed for identification. 2D gels allowed the detection of 13 carbonylated proteins in the bone marrow; seven of these were identified, with two pairs of the same protein. Baseline levels of carbonylation were found in 78 kDa glucose-related protein, heat shock protein cognate 71 KDa, actin, chitinase-like protein 3 (CHI3L1), and carbonic anhydrase 2 (CAII). Radiation increased carbonylation in four proteins, including CHI3L1 and CAII, and induced carbonylation of one additional protein (not identified). Our findings indicate that the profile of specific protein carbonylation in bone marrow is substantially altered by ionizing radiation. Accordingly, protein oxidation may be a mechanism for reduced cell viability.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bone Marrow Protein Oxidation in Response to Ionizing Radiation in C57BL/6J Mice

et al. 2014

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“…Genes related to cell proliferation and/or cell death were selected on the basis of their expression level from two sets of microarray data from bone marrow cells, obtained previously (Hirabayashi and Inoue, , ); i.e. one from the senescence profile (data from 21‐month‐old mice compared with those from 2‐month‐old mice) and the other from the subacute radiation profile (data from mice irradiated at 8 weeks of age, i.e.…”

Section: Resultsmentioning

confidence: 96%

“…Accordingly, it was noted that an increase in the expression level of the marker of intracytoplasmic oxidative stress level with aging played a role in the additional increase in oxidative stress with radiation exposure. In addition, exposure to chemicals such as benzene also induces oxidative stress, but distinct differences between the biological responses induced by radiation exposure and those induced by chemical exposure, can be seen, as described elsewhere (Hirabayashi and Inoue, ).…”

Section: Discussionmentioning

confidence: 99%

Experimentally induced, synergistic late effects of a single dose of radiation and aging: significance in LKS fraction as compared with mature blood cells

Hirabayashi

Tsuboi

Nakachi

et al. 2014

J of Applied Toxicology

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The number of murine mature blood cells recovered within 6 weeks after 2-Gy whole-body irradiation at 6 weeks of age, whereas in the case of the undifferentiated hematopoietic stem/progenitor cell (HSC/HPC) compartment [cells in the lineage-negative, c-kit-positive and stem-cell-antigen-1-positive (LKS) fraction], the numerical differences between mice with and without irradiation remained more than a year, but conclusively the cells showed numerical recovery. When mice were exposed to radiation at 6 months of age, acute damages of mature blood cells were rather milder probably because of their maturation with age; but again, cells in the LKS fraction were specifically damaged, and their numerical recovery was significantly delayed probably as a result of LKS-specific cellular damages. Interestingly, in contrast to the recovery of the number of cells in the LKS fraction, their quality was not recovered, which was quantitatively assessed on the basis of oxidative-stress-related fluorescence intensity. To investigate why the recovery in the number of cells in the LKS fraction was delayed, expression levels of genes related to cellular proliferation and apoptosis of cells in the bone marrow and LKS fraction were analyzed by real-time polymerase chain reaction (RT-PCR). In the case of 21-month-old mice after radiation exposure, Ccnd1, PiK3r1 and Fyn were overexpressed solely in cells in the LKS fraction. Because Ccnd1and PiK3r1 upregulated by aging were further upregulated by radiation, single-dose radiation seemed to induce the acceleration of aging, which is related to the essential biological responses during aging based on a lifetime-dependent relationship between a living creature and xenobiotic materials.

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“…34,35 As a result, the lineage-negative, c-kitpositive, stem cell antigen-positive (LKS) fraction did not recover in 2Gy whole-body irradiated mice. It remained at levels approximately 50-80% of those in age-matched nonirradiated controls until 18 months of age.…”

Section: Apoptosis-related Gene Expression Profiling Of Hematopoieticmentioning

confidence: 99%

The bone marrow niche, stem cells, and leukemia: impact of drugs, chemicals, and the environment

Snyder

2014

Annals of the New York Academy of Sciences

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Hematopoietic stem cells (HSCs) are a unique population of somatic stem cells that can both selfrenew for long-term reconstitution of HSCs and differentiate into hematopoietic progenitor cells, which in turn give rise, in a hierarchical manner, to the entire myeloid and lymphoid lineages. The differentiation and maturation of these lineages occurs in the bone marrow niche, a microenvironment that regulates self-renewal, survival, differentiation, and proliferation, with interactions among signaling pathways in the HSCs and the niche required to establish and maintain homeostasis. The accumulation of genetic mutations and cytogenetic abnormalities within cells of the partially differentiated myeloid lineage, particularly as a result of exposure to benzene or cytotoxic anticancer drugs, can give rise to malignancies like acute myeloid leukemia and myelodysplastic syndrome. Better understanding of the mechanisms driving these malignancies and susceptibility factors, both within hematopoietic progenitor cells and cells within the bone marrow niche, may lead to the development of strategies for prevention of occupational and cancer therapy-induced disease.

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Prediction of Epigenetic and Stochastic Gene Expression Profiles of Late Effects after Radiation Exposure

Cited by 6 publications

References 30 publications

Bone Marrow Protein Oxidation in Response to Ionizing Radiation in C57BL/6J Mice

Bone Marrow Protein Oxidation in Response to Ionizing Radiation in C57BL/6J Mice

Experimentally induced, synergistic late effects of a single dose of radiation and aging: significance in LKS fraction as compared with mature blood cells

The bone marrow niche, stem cells, and leukemia: impact of drugs, chemicals, and the environment

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