Benzene-induced hematopoietic toxicity transmitted by AhR in wild-type mouse and nullified by repopulation with AhR-deficient bone marrow cells: time after benzene treatment and recovery.
Previously, we found an aryl hydrocarbon receptor (AhR)-transmitted benzene-induced hematotoxicity; that is, AhR-knockout (KO) mice did not show any hematotoxicity after benzene exposure [Yoon, B.I., Hirabayashi, Y., Kawasaki, Y., Kodama, Y., Kaneko, T., Kanno, J., Kim, D.Y., Fujii-Kuriyama, Y., Inoue, T., 2002. Aryl hydrocarbon receptor mediates benzene-induced hematotoxicity. Toxicol. Sci. 70, 150-156]. Furthermore, our preliminary study showed a significant attenuation of benzene-induced hematopoietic toxicity by AhR expression, when the bone marrow (BM) of mice was repopulated with AhR-KO BM cells [Hirabayashi, Y., Yoon, B.I., Li, G., Fujii-Kuriyama, Y., Kaneko, T., Kanno, J., Inoue, T., 2005a. Benzene-induced hematopoietic toxicity transmitted by AhR in the wild-type mouse was negated by repopulation of AhR deficient bone marrow cells. Organohalogen Comp. 67, 2280-2283]. In this study, benzene-induced hematotoxicity and its nullification by AhR-KO BM cells were further precisely reevaluated including the duration of the effect after benzene treatment and recovery after the cessation of exposure. Exposure routes, namely, intraperitoneal (i.p.) injection used in our previous study and intragastric (i.g.) administration used in this study, were also compared in terms of their toxicologic outcomes. From the results of this study, mice that had been lethally irradiated and repopulated with BM cells from AhR-KO mice essentially did not show any benzene-induced hematotoxicity. The AhR-KO BM cells nullified benzene-induced toxicities in notably different hematopoietic endpoints between the i.p. treatment and the i.g. treatment; however, the number of granulo-macrophage colony-forming unit in vitro (CFU-GM) was a common target parameter, the benzene-induced toxicity of which was nullified by the AhR-KO BM cells.
Cellular and Molecular Toxicology Division, National Institute of Health Sciences, Tokyo 158-8501, Japan.
Yoko
Y
Hirabayashi
Byung-Il
BI
Yoon
Guang-Xun
GX
Li
Yoshiaki
Y
Fujii-Kuriyama
Toyozo
T
Kaneko
Jun
J
Kanno
Tohru
T
Inoue
D000818:Animals; D001554:Benzene / Q000633:toxicity*; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018336:Receptors, Aryl Hydrocarbon / Q000172:deficiency* / Q000378:metabolism*; D013997:Time Factors
D018336:Receptors, Aryl Hydrocarbon; D001554:Benzene