Gene Expression Profiles in Mouse Liver Cells after Exposure to Different Types of Radiation

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  • ROUDKENAR Mehryar Habibi
    Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University Research Center, Iranian Blood Transfusion Organization Tehran
  • LI Li
    Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University
  • BABA Taisuke
    Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University
  • KUWAHARA Yoshikazu
    Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University
  • NAKAGAWA Hironobu
    Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University
  • WANG Lu
    Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University
  • KASAOKA Satoshi
    Faculty of Pharmaceutical Sciences, Hiroshima International University
  • OHKUBO Yasuhito
    Department of Radiopharmacology, Tohoku Pharmaceutical University
  • ONO Koji
    Radiation Oncology Research Laboratory, Research Reactor Institute, Kyoto University
  • FUKUMOTO Manabu
    Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University

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The liver is one of the target organs of radiation-induced cancers by internal exposures. In order to elucidate radiation-induced liver cancers including Thorotrast, we present a new approach to investigate in vivo effects of internal exposure to α-particles. Adopting boron neutron capture, we separately irradiated Kupffer cells and endothelial cells in mouse liver in vivo and analyzed the changes in gene transcriptions by an oligonucleotide microarray. Differential expression was defined as more than 3-fold for up-regulation and less than 1/3 for under-regulation, compared with non-irradiated controls. Of 6,050 genes examined, 68 showed differential expression compared with non-irradiated mice. Real-time polymerase chain reaction validated the results of the microarray analysis. Exposure to α-particles and γ-rays produced different patterns of altered gene expression. Gene expression profiles revealed that the liver was in an inflammatory state characterized by up-regulation of positive acute phase protein genes, irrespective of the target cells exposed to radiation. In comparison with chemical and biological hepatotoxicants, inductions of Metallothionein 1 and Hemopexin, and suppressions of cytochrome P450s are characteristic of radiation exposure. Anti-inflammatory treatment could be helpful for the prevention and protection of radiation-induced hepatic injury.

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