Polycyclic aromatic hydrocarbons animal models

The goal of this chapter is to stimulate research activity to develop both novel intervention strategies and therapeutic approaches to mitigate the neurotoxicity associated with prenatal exposure to polycyclic aromatic hydrocarbons (PAHs). The focus of this chapter is PAH exposure of vulnerable populations as a result of terrorist attacks on US targets. We will attempt to define the signature of prenatal PAH exposure-induced neurotoxicity within the context of human epidemiological data and translate this to appropriate animals models. 

We are aware too that genetics can play a role in susceptibility. Should one therefore select a sensitive animal model or a resistant one For example, for skin carcinogenesis, the SENCAR mouse is regarded as extremely sensitive to many carcinogens, in particular polycyclic aromatic hydrocarbons. On the other hand, C57 Black mice are insensitive to benzopyrene as an initiator. 

Polycyclic aromatic hydrocarbons are potent immunosuppressive environmental contaminants. Immunotoxic effects of PAHs, which may contribute to their carcinogenic potential, have been established in various animal models and in human immune cells (van Grevenynghe et al., 2004). Inhibition of the production of immunocompetent cells (lymphocytes and monocytes) is likely one of the mechanisms contributing to the immunosuppression due to PAHs. Exposure to PAHs inhibits the differentiation of monocytes into dendritic cells and macrophages it also induces apoptosis of both pre-T cells in the thymus and pre-B cells in the bone marrow, which may account for thymic atrophy and decreased lymphoid cell recovery from the spleen, lymph nodes, and bone marrow in PAH-exposed mice (Lutz et al., 1998 Page et al., 2002). These toxic effects towards precursors of immune cells have been linked, at least in part, to the PAHs metabolism into toxic reactive intermediates triggering apoptosis of pre-B eells (Mann et al., 1999). 

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