title: Assessment of benzene-induced hematotoxicity using a human-like hematopoietic lineage in NOD/Shi-scid/IL-2Rγnull mice.
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-2Rγ(null) (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.
authors.affiliation: Biological Environment Sector, Environmental Science Research Laboratory, Central Research Institute of Electric Power Industry, Chiba, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Tsujimura
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yoshino
authors.forename: Masahito
authors.initials: M
authors.lastname: Hosokawa
authors.forename: Kensuke
authors.initials: K
authors.lastname: Otsuka
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsunaga
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nakasono
mesh_terms: D000818:Animals; D001554:Benzene / Q000633:toxicity*; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID
chemical_list: D053631:Interleukin Receptor Common gamma Subunit; D001554:Benzene