Administration of an Antioxidant Prevents Lymphoma Development in Transmitochondrial Mice Overproducing Reactive Oxygen Species Administration of an Antioxidant Prevents Lymphoma Development in Transmitochondrial Mice Overproducing Reactive Oxygen Species

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Author(s)

    • NAKADA Kazuto
    • Faculty of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan|International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan|Life Science Center of Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan
    • HAYASHI Jun-Ichi
    • Faculty of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan|International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan|Life Science Center of Tsukuba Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan

Abstract

Because of the difficulty to exclude possible involvement of nuclear DNA mutations, it has been a controversial issue whether pathogenic mutations in mitochondrial DNA (mtDNA) and the resultant respiration defects are involved in tumor development. To address this issue, our previous study generated transmitochondrial mice (mito-mice-ND6<sup>13997</sup>), which possess the nuclear and mtDNA backgrounds derived from C57BL/6J (B6) strain mice except that they carry B6 mtDNA with a G13997A mutation in the <i>mt-Nd6</i> gene. Because aged mito-mice-ND6<sup>13997</sup> simultaneously showed overproduction of reactive oxygen species (ROS) in bone marrow cells and high frequency of lymphoma development, current study examined the effects of administrating a ROS scavenger on the frequency of lymphoma development. We used <i>N</i>-acetylcysteine (NAC) as a ROS scavenger, and showed that NAC administration prevented lymphoma development. Moreover, its administration induced longevity in mito-mice-ND6<sup>13997</sup>. The gene expression profiles in bone marrow cells indicated the upregulation of the <i>Fasl</i> gene, which can be suppressed by NAC administration. Given that natural-killer (NK) cells mediate the apoptosis of various tumor cells via enhanced expression of genes encoding apoptotic ligands including <i>Fasl</i> gene, its overexpression would reflect the frequent lymphoma development in bone marrow cells. These observations suggest that continuous administration of an antioxidant would be an effective therapeutics to prevent lymphoma development enhanced by ROS overproduction.

Journal

  • Proceedings of The Japanese Society of Animal Models for Human Diseases

    Proceedings of The Japanese Society of Animal Models for Human Diseases 63(4), 459-466, 2014

    Japanese Association for Laboratory Animal Science

Codes

  • NII Article ID (NAID)
    130005089325
  • NII NACSIS-CAT ID (NCID)
    AA11032321
  • Text Lang
    EN
  • Article Type
    journal article
  • ISSN
    1341-1357
  • NDL Article ID
    025857916
  • NDL Call No.
    Z54-H752
  • Data Source
    NDL  IR  J-STAGE 
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