Frouin Héloïse, Lebeuf Michel, Saint-Louis Richard, Hammill Mike, Pelletier Emilien, Fournier Michel
Institut National de Recherche Scientifique - Institut Armand-Frappier, Laval, Quebec H7V 1B7, Canada.
Aquat Toxicol. 2008 Nov 21;90(3):243-51. doi: 10.1016/j.aquatox.2008.09.005. Epub 2008 Sep 12.
The widespread environmental contamination, bioaccumulation and endocrine disruptor effects of butyltins (BTs) to wildlife are well documented. Although suspected, potential effects of BTs exposure on the immune system of marine mammals have been little investigated. In this study, we assessed the effects of tributyltin (TBT) and its dealkylated metabolites dibutyltin (DBT) and monobutyltin (MBT) on the immune responses of harbour seals. Peripheral blood mononuclear cells isolated from pup and adult harbour seals were exposed in vitro to varying concentrations of BTs. DBT resulted in a significant decrease at 100 and 200 nM of phagocytotic activity and reduced significantly phagocytic efficiency at 200 nM in adult seals. There was no effect in phagocytosis with TBT and MBT. In pups, the highest concentration (200 nM) of DBT inhibited phagocytic efficiency. A reduction of tumor-killing capacity of adult natural killer (NK) cells occurred when leukocytes were incubated in vitro with 50 nM DBT and 200 nM TBT for 24h. In adult seals, T-lymphocyte proliferation was significantly suppressed when the cells were exposed to 200 nM TBT and 100 nM DBT. In pups, the proliferative response increased after an exposure to 100 nM TBT and 50 nM DBT, but decreased with 200 nM TBT and 100 nM DBT. The immune functions were more affected by BTs exposure in adults than in pups, suggesting that other unsuspected mechanisms could trigger immune parameters in pups. The toxic potential of BTs followed the order of DBT>TBT>MBT. BT concentrations of harbour seal pups from the St. Lawrence Estuary (Bic National Park) ranged between 0.1-0.4 ng Sn/g wet weight (ww) and 1.2-13.4 ng Sn/g ww in blood and blubber, respectively. For these animals, DBT concentrations were consistently below the quantification limit of 0.04 ng Sn/g ww in blood and 0.2 ng Sn/g ww in blubber. Results suggest that concentrations measured in pups are considered too low to induce toxic effects to their immune system during first days of life. However, based on our in vitro results, we hypothesize that BTs, and DBT in particular, could pose a serious threat to the immune functions in free-ranging harbour seal adults.
丁基锡（BTs）对野生动物的广泛环境污染、生物累积及内分泌干扰效应已有充分记载。尽管存在怀疑，但BTs暴露对海洋哺乳动物免疫系统的潜在影响却鲜有研究。在本研究中，我们评估了三丁基锡（TBT）及其脱烷基代谢产物二丁基锡（DBT）和单丁基锡（MBT）对港海豹免疫反应的影响。从幼年和成年港海豹分离出的外周血单核细胞在体外暴露于不同浓度的BTs。DBT在100和200 nM时导致成年海豹吞噬活性显著降低，在200 nM时吞噬效率显著降低。TBT和MBT对吞噬作用无影响。在幼崽中，DBT的最高浓度（200 nM）抑制了吞噬效率。当白细胞在体外与50 nM DBT和200 nM TBT孵育24小时后，成年自然杀伤（NK）细胞的肿瘤杀伤能力降低。在成年海豹中，当细胞暴露于200 nM TBT和100 nM DBT时，T淋巴细胞增殖受到显著抑制。在幼崽中，暴露于100 nM TBT和50 nM DBT后增殖反应增加，但在200 nM TBT和100 nM DBT时降低。与幼崽相比，成年海豹的免疫功能受BTs暴露的影响更大，这表明其他未被怀疑的机制可能触发幼崽的免疫参数。BTs的毒性潜力顺序为DBT>TBT>MBT。圣劳伦斯河口（比克国家公园）的港海豹幼崽血液和脂肪中的BT浓度分别在0.1 - 0.4 ng Sn/g湿重（ww）和1.2 - 13.4 ng Sn/g ww之间。对于这些动物，血液中DBT浓度始终低于0.04 ng Sn/g ww的定量限，脂肪中低于0.2 ng Sn/g ww。结果表明，幼崽体内测得的浓度被认为过低，在其生命的最初几天不会对其免疫系统产生毒性作用。然而，基于我们的体外实验结果，我们推测BTs，尤其是DBT，可能对自由放养的成年港海豹的免疫功能构成严重威胁。
