Department of Bioscience, Arctic Research Centre, Aarhus University , Frederiksborgvej 399, PO Box 358, DK-4000 Roskilde, Denmark.
Department of Pathobiology and Veterinary Science, University of Connecticut , 61 North Eagleville Road, Storrs, Connecticut 06269-3089, United States of America.
Environ Sci Technol. 2017 Oct 3;51(19):11431-11439. doi: 10.1021/acs.est.7b03532. Epub 2017 Sep 25.
Most controlled toxicity studies use single chemical exposures that do not represent the real world situation of complex mixtures of known and unknown natural and anthropogenic substances. In the present study, complex contaminant cocktails derived from the blubber of polar bears (PB; Ursus maritimus) and killer whales (KW; Orcinus orca) were used for in vitro concentration-response experiments with PB, cetacean and seal spp. immune cells to evaluate the effect of realistic contaminant mixtures on various immune functions. Cytotoxic effects of the PB cocktail occurred at lower concentrations than the KW cocktail (1 vs 16 μg/mL), likely due to differences in contaminant profiles in the mixtures derived from the adipose of each species. Similarly, significant reduction of lymphocyte proliferation occurred at much lower exposures in the PB cocktail (EC: 0.94 vs 6.06 μg/mL; P < 0.01), whereas the KW cocktail caused a much faster decline in proliferation (slope: 2.9 vs 1.7; P = 0.04). Only the KW cocktail modulated natural killer (NK) cell activity and neutrophil and monocyte phagocytosis in a concentration- and species-dependent manner. No clear sensitivity differences emerged when comparing cetaceans, seals and PB. Our results showing lower effect levels for complex mixtures relative to single compounds suggest that previous risk assessments underestimate the effects of real world contaminant exposure on immunity. Our results using blubber-derived contaminant cocktails add realism to in vitro exposure experiments and confirm the immunotoxic risk marine mammals face from exposure to complex mixtures of environmental contaminants.
大多数毒性控制研究使用单一的化学暴露，这些暴露不能代表真实世界中已知和未知的天然和人为物质的复杂混合物的情况。在本研究中，使用源自北极熊（Ursus maritimus）和虎鲸（Orcinus orca）的鲸脂衍生的复杂污染物混合物进行体外浓度反应实验，研究了真实污染物混合物对各种免疫功能的影响。与 KW 混合物（1 对 16 μg/mL）相比，PB 混合物的细胞毒性作用发生在较低的浓度下（1 对 16 μg/mL），这可能是由于混合物中污染物的特征在每个物种的脂肪中存在差异。同样，在 PB 混合物中，淋巴细胞增殖的显著减少发生在低得多的暴露水平下（EC：0.94 对 6.06 μg/mL；P < 0.01），而 KW 混合物导致增殖迅速下降（斜率：2.9 对 1.7；P = 0.04）。只有 KW 混合物以浓度和物种依赖的方式调节自然杀伤（NK）细胞活性以及中性粒细胞和单核细胞吞噬作用。当比较鲸类、海豹和 PB 时，没有出现明显的敏感性差异。我们的结果表明，与单一化合物相比，复杂混合物的效应水平较低，这表明先前的风险评估低估了真实世界污染物暴露对免疫的影响。我们使用源自鲸脂的污染物混合物的结果增加了体外暴露实验的现实性，并证实了海洋哺乳动物因暴露于环境污染物的复杂混合物而面临的免疫毒性风险。
