论文部分内容阅读
目的多氯联苯(polychlorinated biphenyls,PCBs)是一类具有重要毒理学作用的持久性有机污染物,经肝脏代谢可形成羟基多氯联苯(hydroxylated polychlorinated biphenyls,OH-PCBs);本研究旨在探讨OH-PCBs对大鼠磺基转移酶(SULT)1A1和SULT2A3活性的影响。方法大鼠SULT1A1和SULT2A3分别从重组表达的大肠杆菌制备,以亲和层析法纯化;在SULT1A1和SULT2A3催化其底物2-萘酚和脱氢表雄酮形成硫酸基结合物(以3’,5’-二磷酸腺苷的形成测定酶活性)的基础上,观察7个OH-PCBs对上述反应的影响。结果受试物均能明显抑制大鼠SULT1A1活性,尤以3,5-二氯-4-羟基结构的OH-PCBs作用(以半数抑制浓度衡量)作用强度为高。相反,各受试OH-PCBs对大鼠SULT2A3缺乏强烈作用,仅3个化合物在溶解度范围达到对其完全抑制。结论 OH-PCBs可能选择性抑制大鼠SULT中的SULT1A1亚型,而3,5-二氯-4-羟基结构与特别强的抑制作用有关。本研究结果提示在PCBs染毒大鼠的试验中SULT1A1的作用可能受到抑制。
PURPOSE Polychlorinated biphenyls (PCBs) are a class of persistent organic pollutants that have important toxicological effects and are metabolized by the liver to form hydroxylated polychlorinated biphenyls (OH-PCBs). The aim of this study To investigate the effects of OH-PCBs on the activity of sulfotransferases (SULT) 1A1 and SULT2A3 in rats. METHODS: SULT1A1 and SULT2A3 were respectively prepared from recombinant E. coli and purified by affinity chromatography. SULT1A1 and SULT2A3 catalyzed the formation of sulfate-based conjugates of 2-naphthol and dehydroepiandrosterone at 3 ’ , 5’-diphosphate adenosine formation assay enzyme activities) based on the observed seven OH-PCBs on the reaction. Results All the tested substances could obviously inhibit the activity of SULT1A1 in rats, especially the action of OH-PCBs (measured by half-inhibitory concentration) of 3,5-dichloro-4-hydroxy structure. In contrast, each of the OH-PCBs tested lacked a strong effect on SULT2A3 in rats, and only three of the compounds achieved their complete inhibition in the solubility range. Conclusion OH-PCBs may selectively inhibit the SULT1A1 subtype in rat SULT, while the 3,5-dichloro-4-hydroxy structure is associated with a particularly strong inhibitory effect. Our results suggest that SULT1A1 may be inhibited in the PCBs-exposed rats.