Assessment of Benzene-Induced Hematotoxicity Using a Human-Like Hematopoietic Lineage in NOD-Shi-scid-IL-2Rγnull MiceReport as inadecuate




Assessment of Benzene-Induced Hematotoxicity Using a Human-Like Hematopoietic Lineage in NOD-Shi-scid-IL-2Rγnull Mice - Download this document for free, or read online. Document in PDF available to download.

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.



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

Source: http://plos.srce.hr/



DOWNLOAD PDF




Related documents