Department of Pharmacology and Toxicology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298, USA.
J Immunotoxicol. 2010 Jul-Sep;7(3):219-31. doi: 10.3109/1547691X.2010.487193.
1,2:5,6-Dibenzanthracene (DBA) is ubiquitous in our environment as a contaminant produced by incomplete combustion of organics from sources such as forest fires, cigarette smoke, and asphalt paving, and it is more immunosuppressive of the T-dependent antibody-forming cell (AFC) response than the well-studied polycyclic aromatic hydrocarbon, benzo(a)pyrene. The systemic immunosuppressive effects of DBA were investigated following a single pharyngeal aspiration (pa) in female B(6)C(3)F(1) mice. The immunotoxic effects of DBA were evaluated using numerous assays of varying complexity to evaluate innate (natural killer [NK] cell activity), cell-mediated (T-lymphocyte proliferation, mixed leukocyte response [MLR], cytotoxic T-lymphocyte [CTL] activity, delayed-type hypersensitivity [DTH]), and humoral immunity (B-lymphocyte proliferation, T-dependent antibody responses). A single pa of DBA at doses up to 30 mg/kg had no effect on NK cell activity, anti-CD3 antibody-mediated T-lymphocyte proliferation, the MLR, or B-lymphocyte proliferation. DBA at 30 mg/kg suppressed Concanavalin A (ConA)-stimulated T-lymphocyte proliferation and the CTL response. DBA exposure reduced cytokine production in spleen cell culture supernatants after in vitro stimulation with ConA or lipopolysaccharide (LPS). Immunosuppression was observed at lower doses in the holistic assays. The DTH response to Candida albicans was significantly decreased at 3.0 mg/ kg DBA, while the AFC response was intermittently suppressed at 1.0 mg/kg, with no effect observed at 0.3 mg/kg. These results demonstrate that a single pa of DBA produces systemic immunotoxicity, and of the assays utilized, the holistic assays (i.e., DTH, AFC) appear to be most sensitive to the immunosuppressive effects of DBA.
1,2:5,6-二苯并蒽(DBA)是一种普遍存在于环境中的污染物,它是由森林火灾、香烟烟雾和沥青铺路等来源的有机物不完全燃烧产生的。与研究充分的多环芳烃苯并(a)芘相比,它对 T 依赖性抗体形成细胞(AFC)反应的免疫抑制作用更强。通过雌性 B(6)C(3)F(1)小鼠单次咽吸(pa)研究了 DBA 的全身免疫抑制作用。使用多种不同复杂程度的检测方法评估了 DBA 的免疫毒性作用,以评估先天(自然杀伤[NK]细胞活性)、细胞介导(T 淋巴细胞增殖、混合白细胞反应[MLR]、细胞毒性 T 淋巴细胞[CTL]活性、迟发型超敏反应[DTH])和体液免疫(B 淋巴细胞增殖、T 依赖性抗体反应)。单次 pa 给予高达 30 mg/kg 的 DBA 对 NK 细胞活性、抗 CD3 抗体介导的 T 淋巴细胞增殖、MLR 或 B 淋巴细胞增殖没有影响。30 mg/kg 的 DBA 抑制了 Concanavalin A(ConA)刺激的 T 淋巴细胞增殖和 CTL 反应。DBA 暴露降低了体外用 ConA 或脂多糖(LPS)刺激脾细胞培养上清液中的细胞因子产生。在整体检测中,较低剂量时观察到免疫抑制作用。3.0 mg/kg DBA 时,对白念珠菌的 DTH 反应显著降低,而 1.0 mg/kg 时 AFC 反应间歇性受抑制,0.3 mg/kg 时未观察到。这些结果表明,单次 pa 的 DBA 会导致全身免疫毒性,在使用的检测方法中,整体检测(即 DTH、AFC)似乎对 DBA 的免疫抑制作用最敏感。