Regala R P, Rice C D, Schwedler T E, Dorociak I R
Department of Environmental Toxicology, P.O. Box 709, Clemson University, Pendleton, South Carolina 29670, USA.
Arch Environ Contam Toxicol. 2001 Apr;40(3):386-91. doi: 10.1007/s002440010187.
The organotin tributyltin (TBT) is an antifouling biocide used in marine paints and is a common pollutant in harbor estuaries. We previously demonstrated that the immune system of channel catfish, Ictalurus punctatus, is a sensitive target organ of TBT. Exposure strongly suppresses humoral immune responses. Harbor estuaries often contain polychlorinated biphenyls (PCBs) due to their ubuquitous distribution. The coplanar congener 3,3',4,4'5'-polychlorinated biphenyl (PCB-126) is also immunotoxic to channel catfish, but it suppresses only the innate immune responses and only at high doses. In this study we exposed channel catfish to TBT, PCB-126, or both in mixtures, with canola oil (CO) serving as the carrier control. Antibody responses to Vibrio anguillarum and phagocyte oxidative burst activity were measured after (1) a single dose of 0.01 or 1 mg/kg of each or both in combination, and (2) six injections of 1.7 or 170 microg/kg of each (or in combination) given every 3 days over a 16-day period to yield a cumulative dose of 0.01 or 1 mg/kg, respectively. We measured antibody responses to V. anguillarum 21 days after immunization and oxidative burst activities 14 and 21 days after the final treatment. The highest dose of TBT suppressed antibody responses after a single exposure. The high dose of PCB-126 also suppressed antibody responses. The addition of PCB-126 to TBT doses did not alter the antibody responses beyond the effects of TBT alone. In the repeated exposure group, only the high dose of TBT suppressed antibody responses. In animals exposed to mixtures, high levels of PCB-126 enhanced suppression associated with low levels of TBT, whereas PCB-126 protected against suppression associated with high levels of TBT. Single exposures to TBT or PCB-126 suppressed phagocyte oxidative burst activity. In animals exposed to mixtures, as a single exposure, the addition of a low dose PCB-126 protected against low dose TBT-related oxidative burst activity suppression. In the repeated exposure groups TBT suppressed oxidative burst activity, but only at the highest dose on day 21, while high doses of PCB-126 suppressed activity on day 14. Furthermore, low levels of PCB-126 reversed the suppressed oxidative burst activity associated with high levels of TBT on day 21. Overall, this study demonstrates moderate additivity in terms of the immunotoxicity of TBT and PCB-126 mixtures using these two endpoints of immune function in the channel catfish model.
有机锡三丁基锡（TBT）是一种用于船舶涂料的防污杀生剂，是港口河口常见的污染物。我们之前证明，斑点叉尾鮰的免疫系统是TBT的一个敏感靶器官。暴露会强烈抑制体液免疫反应。由于多氯联苯（PCBs）分布广泛，港口河口常常含有这种物质。共面同系物3,3',4,4',5'-多氯联苯（PCB - 126）对斑点叉尾鮰也具有免疫毒性，但仅在高剂量时才会抑制先天免疫反应。在本研究中，我们将斑点叉尾鮰暴露于TBT、PCB - 126或两者的混合物中，以菜籽油（CO）作为载体对照。在（1）单次给予每一种或两者组合剂量为0.01或1 mg/kg后，以及（2）在16天内每3天注射一次，每次注射1.7或170 μg/kg每一种（或组合），以分别产生累积剂量0.01或1 mg/kg后，测量对鳗弧菌的抗体反应和吞噬细胞氧化爆发活性。我们在免疫后21天测量对鳗弧菌的抗体反应，在最后一次处理后14天和21天测量氧化爆发活性。单次暴露后，最高剂量的TBT抑制了抗体反应。高剂量的PCB - 126也抑制了抗体反应。在TBT剂量中添加PCB - 126并没有改变抗体反应，其影响不超过单独TBT的作用。在重复暴露组中，只有高剂量的TBT抑制了抗体反应。在暴露于混合物的动物中，高浓度的PCB - 126增强了与低浓度TBT相关的抑制作用，而PCB - 126则防止了与高浓度TBT相关的抑制作用。单次暴露于TBT或PCB - 126会抑制吞噬细胞氧化爆发活性。在单次暴露于混合物的动物中，添加低剂量的PCB - 126可防止低剂量TBT相关的氧化爆发活性抑制。在重复暴露组中，TBT抑制了氧化爆发活性，但仅在第21天的最高剂量时出现，而高剂量的PCB - 126在第14天抑制了活性。此外，低浓度的PCB - 126在第21天逆转了与高浓度TBT相关的氧化爆发活性抑制。总体而言，本研究使用斑点叉尾鮰模型中免疫功能的这两个终点，证明了TBT和PCB - 126混合物在免疫毒性方面具有中等加和性。
