Immunomodulation by Dibenz(a,h)anthracene in B6C3F1 Mice

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DESCRIPTION (provided by applicant): Dibenz(a,h)anthracene (DBA) is an environmental contaminant listed on the EPA's priority pollutant list and has been observed to immunosuppress humoral, innate and cell-mediated immune responses. The humoral immune response, as evaluated by the IgM Antibody Forming Cell (AFC) assay, has previously been demonstrated as the most sensitive to DBA exposure in adult animals. Using adult B6C3F1 mice, evaluation of the mechanism of action of DBA on the AFC following subcutaneous exposure for 28 days will be pursued. Additionally, evaluation of the qualitative, quantitative and persistent effects of developmentally exposing animals to DBA will also be performed by evaluating the female F1 generation of C57BI6 females and C3H males. Pups will be exposed in utero and through lactation, followed by evaluation at 6 or 15 weeks of age. Numerous findings in the scientific literature have demonstrated the increased susceptibility of the developing immune system to xenobiotic exposure when compared to adult exposure data. Therefore, the in vitro AFC assay will be utilized to evaluate the cellular and subcellular mechanisms leading to the immunotoxicity observed with exposure to DBA in adult and F1 animals.