Wirth Jena R, Peden-Adams Margie M, White Natasha D, Bossart Gregory D, Fair Patricia A
Graduate Program in Marine Biology, College of Charleston, 205 Fort Johnson Road, Charleston, SC, 29412, USA.
J Appl Toxicol. 2014 Jun;34(6):658-66. doi: 10.1002/jat.2891. Epub 2013 May 30.
Previous studies in our lab have shown that perfluorooctane sulfonate (PFOS) modulates immune function in mice and correlates with many immune parameters in bottlenose dolphins (Tursiops truncatus). In this study, bottlenose dolphin peripheral blood leukocytes (PBLs) and adult female B6C3F1 mouse splenocytes were exposed to environmentally relevant PFOS concentrations (0-5 µg ml(-1)) in vitro; and natural killer (NK) cell activity and lymphocyte proliferation (T and B cell) were assessed using the parallelogram approach for risk assessment. The objectives were: to corroborate results from the correlative studies in bottlenose dolphins with in vitro PFOS exposures; to evaluate the sensitivity of the mouse model as compared with bottlenose dolphins; and to assess risk using the parallelogram approach. In mouse cells, NK cell activity was decreased at in vitro doses of 0.01, 0.5, 0.1, 0.5 and 1 µg PFOS ml(-1) and increased at 5 µg ml(-1). Additionally, B cell proliferation was not altered, but T cell proliferation was decreased at all in vitro PFOS exposures. In dolphin cells, NK cell activity and T cell proliferation were not altered by in vitro PFOS exposure, but B cell proliferation exhibited a positive association in relation to PFOS dose. Overall, the data indicates that: the in vitro exposures of bottlenose dolphin PBLs exhibited results similar to reported correlative fields studies; that mice were generally more sensitive (for these selected endpoints) than were dolphins; and that the parallelogram approach could be used two-thirds of the time to predict the effects in bottlenose dolphins.
我们实验室之前的研究表明,全氟辛烷磺酸(PFOS)可调节小鼠的免疫功能,并且与宽吻海豚(瓶鼻海豚)的许多免疫参数相关。在本研究中,将宽吻海豚外周血白细胞(PBLs)和成年雌性B6C3F1小鼠脾细胞在体外暴露于环境相关浓度的PFOS(0 - 5 µg ml(-1));并使用平行四边形方法评估自然杀伤(NK)细胞活性和淋巴细胞增殖(T细胞和B细胞),以进行风险评估。目标是:用体外PFOS暴露来证实宽吻海豚相关研究的结果;评估小鼠模型与宽吻海豚相比的敏感性;并使用平行四边形方法评估风险。在小鼠细胞中,体外剂量为0.01、0.5、0.1、0.5和1 µg PFOS ml(-1)时NK细胞活性降低,而在5 µg ml(-1)时升高。此外,B细胞增殖未改变,但在所有体外PFOS暴露下T细胞增殖均降低。在海豚细胞中,体外PFOS暴露未改变NK细胞活性和T细胞增殖,但B细胞增殖与PFOS剂量呈正相关。总体而言,数据表明:宽吻海豚PBLs的体外暴露结果与已报道的相关现场研究相似;小鼠(对于这些选定的终点)通常比海豚更敏感;并且平行四边形方法在三分之二的时间内可用于预测宽吻海豚的效应。