Mechanism of benzene-induced hematopoietic disturbances mediated by arylhydrocarbon receptors

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Research subject of this report was originally based on a fundamental discovery that the benzene-induced hematopoietic toxicity was nullified in the aryl hydrocarbon receptor (AhR) knockout (KO) mice. Utilizing this as a model, thus, the aim of the research subject was to proceed research on an experimental model for elucidation of mechanism underlying receptor-mediated chemical toxicity.Outcome of the original publications includes an elucidation of unique biological function of AhRs. A cell cycle related study of the hemopoietic stem/progenitor concerns, by the AhR, primitive progenitor cells are maintained in the slower cell cycling with possible dormant fraction, whereas mature progenitor cells are in the faster cell cycling. In AhR knockout mice, benzene exposure has been known not to express p21^<waf1>, cell cycle dependent kinase inhibitor. In this regard, it is of interest that mice carrying human thioredoxin gene over-expressed shows a down modulation of AhR during benzene exposure, which may have a possible relevancy to the attenuation of the benzene-induced hematotoxicity in Trx-Tg mice. Another study related to AhR expression after benzene exposure is to define the possible site of benzene-induced hematotoxicity by means of bone marrow transplantation which shows that the hematotoxicity after benzene exposure is solely from the repopulated AhR deficient bone marrow cells. There seems to be another possibility of benzene-induced peripheral blood toxicity, which is presumably based on the hepatic xenobiotic response other than repopulated bone marrow.Progresses mentioned above are essentially published elsewhere.