Assessment of Benzene-Induced Hematotoxicity Using a Human-Like Hematopoietic Lineage in NOD/Shi-scid/IL-2Rγnull Mice

Masayuki Takahashi, Noriyuki Tsujimura, Tomoko Yoshino, Masahito Hosokawa, Kensuke Otsuka, Tadashi Matsunaga, Satoshi Nakasono

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Despite recent advancements, it is still difficult to evaluate in vivo responses to toxicants in humans. Development of a system that can mimic the in vivo responses of human cells will enable more accurate health risk assessments. A surrogate human hematopoietic lineage can be established in NOD/Shi-scid/IL-2Rγnull (NOG) mice by transplanting human hematopoietic stem/progenitor cells (Hu-NOG mice). Here, we first evaluated the toxic response of human-like hematopoietic lineage in NOG mice to a representative toxic agent, benzene. Flow cytometric analysis showed that benzene caused a significant decrease in the number of human hematopoietic stem/progenitor cells in the bone marrow and the number of human leukocytes in the peripheral blood and hematopoietic organs. Next, we established chimeric mice by transplanting C57BL/6 mouse-derived bone marrow cells into NOG mice (Mo-NOG mice). A comparison of the degree of benzene-induced hematotoxicity in donor-derived hematopoietic lineage cells within Mo-NOG mice indicated that the toxic response of Hu-NOG mice reflected interspecies differences in susceptibilities to benzene. Responses to the toxic effects of benzene were greater in lymphoid cells than in myeloid cells in Mo-NOG and Hu-NOG mice. These findings suggested that Hu-NOG mice may be a powerful in vivo tool for assessing hematotoxicity in humans, while accounting for interspecies differences.

Original languageEnglish
Article numbere50448
JournalPLoS One
Volume7
Issue number12
DOIs
Publication statusPublished - 2012 Dec 3
Externally publishedYes

Fingerprint

benzene
Benzene
Poisons
mice
Hematopoietic Stem Cells
Stem cells
stem cells
Bone
Cells
Health risks
Risk assessment
cells
Bone Marrow
Blood
Myeloid Cells
bone marrow cells
Leukocyte Count
Inbred C57BL Mouse
Bone Marrow Cells
toxic substances

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Takahashi, M., Tsujimura, N., Yoshino, T., Hosokawa, M., Otsuka, K., Matsunaga, T., & Nakasono, S. (2012). Assessment of Benzene-Induced Hematotoxicity Using a Human-Like Hematopoietic Lineage in NOD/Shi-scid/IL-2Rγnull Mice. PLoS One, 7(12), [e50448]. https://doi.org/10.1371/journal.pone.0050448

Assessment of Benzene-Induced Hematotoxicity Using a Human-Like Hematopoietic Lineage in NOD/Shi-scid/IL-2Rγnull Mice. / Takahashi, Masayuki; Tsujimura, Noriyuki; Yoshino, Tomoko; Hosokawa, Masahito; Otsuka, Kensuke; Matsunaga, Tadashi; Nakasono, Satoshi.

In: PLoS One, Vol. 7, No. 12, e50448, 03.12.2012.

Research output: Contribution to journalArticle

Takahashi, M, Tsujimura, N, Yoshino, T, Hosokawa, M, Otsuka, K, Matsunaga, T & Nakasono, S 2012, 'Assessment of Benzene-Induced Hematotoxicity Using a Human-Like Hematopoietic Lineage in NOD/Shi-scid/IL-2Rγnull Mice', PLoS One, vol. 7, no. 12, e50448. https://doi.org/10.1371/journal.pone.0050448
Takahashi, Masayuki ; Tsujimura, Noriyuki ; Yoshino, Tomoko ; Hosokawa, Masahito ; Otsuka, Kensuke ; Matsunaga, Tadashi ; Nakasono, Satoshi. / Assessment of Benzene-Induced Hematotoxicity Using a Human-Like Hematopoietic Lineage in NOD/Shi-scid/IL-2Rγnull Mice. In: PLoS One. 2012 ; Vol. 7, No. 12.
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