Commonality and Stochasticity in Systems Toxicology

Hirabayashi, Yoko; Inoue, Tohru

doi:10.1002/9780470744307.gat227

Cited by 6 publications

(10 citation statements)

References 137 publications

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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: 95%

“…Senescence is conceptually considered to be a xenobiotic response to 'time' throughout the lifetime that includes agerelated accumulation of xenobiotic metabolic products in relation to oxidative stresses, epigenetic senescent damages and changes owing to genomic instability, among others (DePinho, 2000;Golden et al, 2002;Hirabayashi and Inoue, 2011). However, oxidative stress induced by even a single-dose radiation exposure may be involved in these life-long xenobiotic responses, which is not precisely known yet.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Resultsmentioning

confidence: 95%

Section: Introductionmentioning

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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“…In order to clarify the effects of irradiation on the mechanisms of aging, Yoko Hirabayashi (National Institute of Health Sciences, Japan) exposed mice to single whole‐body irradiation and investigated the response of HSCs/HPCs . As a result, the lineage‐negative, c‐kit‐positive, stem cell antigen–positive (LKS) fraction did not recover in 2 Gy whole‐body irradiated mice; it remained at levels approximately 50–80% of those in age‐matched nonirradiated controls until 18 months of age.…”

Section: Stem Cell Signaling and The Nichementioning

confidence: 99%

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

Greim

Kaden

Larson

et al. 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 self-renew 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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“…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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Commonality and Stochasticity in Systems Toxicology

Cited by 6 publications

References 137 publications

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

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

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

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