Benedetti Maura, Fattorini Daniele, Martuccio Giacomo, Nigro Marco, Regoli Francesco
Dipartimento di Biochemica, Biologia e Genetica, Università Politecnica delle Marche, Ancona, Italy.
Environ Toxicol Chem. 2009 Apr;28(4):818-25. doi: 10.1897/08-066.1.
Biological effects of chemical mixtures are an emerging issue when using biomarkers in field conditions, because synergistic or inhibitory interactions, cascade, and indirect mechanisms can both enhance or suppress responses to specific classes of pollutants. The Antarctic rock cod (Trematomus bernacchii) was exposed to various trace metals (Cu, Hg, Ni, and Pb) and to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), dosed alone or in combination, to generate hypotheses regarding the mechanisms of action at the cellular level. Concentrations of metals significantly increased in liver of T. bernacchii without significant differences between organisms exposed only to the elements or cotreated with TCDD. The marked induction of cytochrome P450 (CYP) by TCDD was greatly suppressed by cotreatment with Cu at both catalytic and protein expression levels, whereas no significant effects were caused by coexposures with Hg, Ni, and Pb. The oxidative status was measured by integrating individual antioxidants with the total oxyradical scavenging capacity toward peroxyl radicals (ROO*) and hydroxyl radicals (*OH). Synergistic oxidative effects appeared in fish coexposed to Cu and TCDD, suggesting that biotransformation efficiency is down-regulated by higher levels of hydrogen peroxide, hydroxyl radicals, and/or mechanisms limiting availability of heme groups. Major oxidative perturbations also were observed in organisms coexposed to TCDD and Hg; in these organisms, however, the marked increase of glutathione content could explain the absence of oxidative inhibition of the CYP system. More limited oxidative effects were caused by Ni and Pb, and the contemporary absence of inhibitory effects on CYP would further confirm the importance of pro-oxidant mechanisms in modulating the biotransformation pathway. The overall results indicate that a wide battery of biomarkers is necessary to assess the impact of chemical mixtures in field conditions.
在野外条件下使用生物标志物时，化学混合物的生物效应是一个新出现的问题，因为协同或抑制相互作用、级联反应和间接机制都可能增强或抑制对特定污染物类别的反应。南极岩鳕（Trematomus bernacchii）被单独或组合暴露于各种痕量金属（铜、汞、镍和铅）以及2,3,7,8-四氯二苯并对二恶英（TCDD），以生成关于细胞水平作用机制的假设。南极岩鳕肝脏中的金属浓度显著增加，仅暴露于这些元素或与TCDD共同处理的生物体之间没有显著差异。在催化和蛋白质表达水平上，与铜共同处理极大地抑制了TCDD对细胞色素P450（CYP）的显著诱导，而与汞、镍和铅共同暴露则没有显著影响。通过将单个抗氧化剂与对过氧自由基（ROO*）和羟基自由基（*OH）的总氧自由基清除能力相结合来测量氧化状态。在同时暴露于铜和TCDD的鱼类中出现了协同氧化效应，这表明生物转化效率因过氧化氢、羟基自由基水平升高和/或限制血红素基团可用性的机制而被下调。在同时暴露于TCDD和汞的生物体中也观察到了主要的氧化扰动；然而，在这些生物体中，谷胱甘肽含量的显著增加可以解释CYP系统没有受到氧化抑制的原因。镍和铅引起的氧化效应较为有限，同时对CYP没有抑制作用将进一步证实促氧化机制在调节生物转化途径中的重要性。总体结果表明，需要大量的生物标志物来评估野外条件下化学混合物的影响。
