Polycyclic’ Aromatic Hydrocarbon Induced Intracellular Signaling and Lymphocyte Apoptosis

Alexander M. Schneider

    Publikation: Bog/antologi/afhandling/rapportPh.d.-afhandlingForskning

    Abstract

    The aryl hydrocarbon (dioxin) receptor (AhR) is a transcription factor possessing high affinity to potent environmental pollutants, polycyclic aromatic hydrocarbons (PAH) and related halogenated hydrocarbons (e.g. dioxins). Numerous research attribute toxicity of these compounds to the receptor mediated events. It raises the question,” Which addit’ ronal transcription factors does the AhR interact with?” In the present work, the hypothesis was postulated and tested that the AhR ligated with PAH activates cytoplasmic NP-KB. This suggests a number of new toxic outcomes for PAH exposures, and offers novel mechanistic explanations for the toxicity of the known compounds. Another unanswered question of the AhR biochemistry is,” Which factors do control the AhP expression and activity?” Using fibroblast model, the role of a cell cycle in maintaining the AhR level was evaluated. The results of this research indicate that the AhR is controlled by the cell progression through the cell cycle. This may imply differential cellular sensitivity to the toxins, and a role for the AhR in cell growth/differentiation. Previous PAH inununotoxicity research did not adequately address effects on immature lymphocytes. Our experiments on preB lymphocytes supported by stromal cells suggest that apoptosis is one of the mechanisms for PAH immunosuppression. It could be either due to direct effect of the PAH on the B cells, via stromal cell signaling. Ubiquitous PAH-like toxin, fluoranthene, was tested for it’s ability to initiate apoptosis in T cell hybridomas. Our data demonstrate that PAH may induce apoptosis and innnunotoxicity in T cell branch of immune system. The mechanism of this process seems to be the AhR independent, and mediated by Ca
    OriginalsprogEngelsk
    UdgivelsesstedRoskilde
    ForlagRoskilde Universitet
    Antal sider119
    StatusUdgivet - 1998

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