Department of Microbiology and Immunology, Creighton University, Omaha, NE, 68178, USA.
Department of Environment and Geography, University of York, Heslington, York, YO10 5NG, United Kingdom.
Chemosphere. 2021 Feb;264(Pt 1):128420. doi: 10.1016/j.chemosphere.2020.128420. Epub 2020 Sep 23.
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a toxic and persistent organic pollutant found in soils and sediments. It has been linked to several adverse health outcomes in humans and wildlife, including suppression of the immune system. TCDD is strongly sorbed to soils/sediments due to its extremely low water solubility. Presently, the bioavailability of soil/sediment-sorbed TCDD to mammals is not completely understood. Our previous studies demonstrated that TCDD adsorbed to representative inorganic geosorbents (i.e. porous silica and smectite clay) exhibited the same bioavailability to mice as TCDD dissolved in corn oil, whereas sequestration by activated carbons eliminated TCDD bioavailability. In this study, we evaluated the effects of amorphous natural organic matter (NOM), primarily in the form of aquatic humic and fulvic acids, on the mouse bioavailability of TCDD. An aqueous suspension of TCDD mixed with NOM was administered to mice via oral gavage. The relative bioavailability of TCDD was assessed by two sensitive aryl hydrocarbon receptor-mediated responses in mice: 1) hepatic induction of cyp1A1 mRNA; and 2) suppression of immunoglobulin M (IgM) antibody-forming cell (AFC) response which is an indicator of immunotoxicity. Hepatic induction of cyp1A1 mRNA and suppression of IgM AFC induced by TCDD were similar in the NOM-sorbed form and dissolved in corn oil, revealing no loss of bioavailability when associated with NOM. Hence, NOM-associated TCDD is as capable of suppressing humoral immunity in mice as TCDD dissolved in corn oil, indicating that NOM-sorbed TCDD is likely to fully retain its bioavailability to mammals and, by inference, humans.
2,3,7,8-四氯二苯并对二恶英(TCDD)是一种存在于土壤和沉积物中的有毒且持久性有机污染物。它已被证明与人类和野生动物的几种不良健康后果有关,包括免疫系统抑制。由于 TCDD 的极低水溶性,它会强烈被土壤/沉积物吸附。目前,哺乳动物对土壤/沉积物吸附的 TCDD 的生物可利用性尚不完全清楚。我们之前的研究表明,吸附在代表性无机地球化学吸附剂(即多孔二氧化硅和蒙脱石粘土)上的 TCDD 对小鼠的生物可利用性与溶解在玉米油中的 TCDD 相同,而活性炭的隔离则消除了 TCDD 的生物可利用性。在这项研究中,我们评估了无定形天然有机物(NOM),主要以水合腐殖酸和富里酸的形式,对 TCDD 小鼠生物利用度的影响。通过口服灌胃将 TCDD 的水悬浮液与 NOM 混合施用于小鼠。通过两种敏感的芳烃受体介导的小鼠反应评估 TCDD 的相对生物利用度:1)肝 CYP1A1 mRNA 的诱导;2)抑制免疫球蛋白 M(IgM)抗体形成细胞(AFC)反应,这是免疫毒性的指标。TCDD 诱导的 Cyp1A1 mRNA 肝诱导和 IgM AFC 抑制在 NOM 吸附形式和溶解在玉米油中相似,表明与 NOM 结合时没有生物利用度损失。因此,与 NOM 结合的 TCDD 与溶解在玉米油中的 TCDD 一样能够抑制小鼠的体液免疫,这表明 NOM 吸附的 TCDD 可能完全保留其对哺乳动物(进而推断对人类)的生物利用度。