Study on the signal cross talk bencath the Arythydroearbon receptor in the hemopoietic stem cells.

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Arylhydrocarbon receptor (Ah R), molecular weight about 90,000, cloned by Burbach et al Hoffman, et al., and Ema, et al. (1991 though 1992) was Identified to be a "xenobiotic ele'ments-recognizmg receptor protein", consisting basic helix-loop-helix transcription sequence, of which physiological ligands are not known. The xenobioticresponsive element has been identified in the express, on regulatory region of the thioredoxin gene ; Consequently, AhR has been assumed to respond to an in vivo-oxidation. In this study, first, in the Ah R-knockout (KO) mouse, a cell cycle was accelerated in the immature fraction ofhemopoietic stem cells, whereas it was decelerated in the well differentiated progenitor cells, when AhR-signal is knocked out, where signals from physiological ligands are deficient for suppressing cell cycle. Second, the hematotoxicity due to benzene-inhalation that induces oxidative stress, was attenuated in the AhR KO mice Third, upregulation of p21 after benzene exposure regularly seen in the wild-type mice was not observed in AhR KO mice, implying the benzene toxicity may be transmitted through the Ah RIn conclusion, oxidative stress induced by benzene inhalation was identified to be attenuated when thioredoxin gene was over-expressed. All of the findings namely discovered during the studying project published are attached in the separate publication brochure. Future proposal of the present study is to identify those responsible molecules, participating those signal pathways, including metabolic enzymes, related to hemopoietic suppression after benzene exposure.