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

描述(由申请人提供)：二苯并(a，h)菲(DBA)是环保局优先污染物清单上列出的一种环境污染物，已被观察到会抑制体液、天然和细胞介导的免疫反应。通过IgM抗体形成细胞(AFC)试验评估的体液免疫反应，以前在成年动物中被证明是对DBA暴露最敏感的。使用成年B6C3F1小鼠，将继续评估DBA对皮下暴露28天后AFC的作用机制。此外，还将通过评估C57BI6雌性和C3H雄性的雌性F1代来评估动物发育过程中暴露于DBA的定性、定量和持续影响。幼崽将在子宫和哺乳期暴露，然后在6或15周大时进行评估。科学文献中的大量发现表明，与成人接触数据相比，发育中的免疫系统对异物暴露的易感性增加。因此，体外AFC试验将被用来评估导致成年和F1动物暴露于DBA的免疫毒性的细胞和亚细胞机制。

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.