Qin Guohua, Meng Ziqiang
Institute of Environmental Medicine and Toxicology, Shanxi University, Taiyuan 030006, China.
Regul Toxicol Pharmacol. 2006 Jun;45(1):36-43. doi: 10.1016/j.yrtph.2006.02.006. Epub 2006 Apr 17.
Sulfur dioxide (SO2) is a ubiquitous air pollutant, present in low concentrations in the urban air, and in higher concentrations in the working environment. Benzo(a)pyrene (B(a)P), a polycyclic aromatic hydrocarbon, is a ubiquitous environmental contaminant with diverse toxicological effects. To investigate the interactions between SO2 and B(a)P, male Wistar rats were exposed to intratracheally instilled with benzo(a)pyrene (B(a)P; 3 mg) or SO2 (20 ppm) inhalation alone or together. The mRNA of CYP1A1 and 1A2, c-fos, and c-jun and protein levels of c-fos and c-jun were analyzed in lungs using a real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) assay and Western blot analysis, respectively. And 7-ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD) activities were detected. In lungs of rats exposed to SO2 alone, the gene transcription of CYP1A1 and 1A2, the EROD and MROD activities were decreased. Meanwhile, the mRNA and protein levels of c-jun and c-fos were increased significantly. Exposure to B(a)P alone induced CYP1A1, CYP1A2 mRNA levels, the protein levels of c-jun, and the EROD and MROD activities in lungs. However, exposure to B(a)P plus inhaled SO2 neither increased nor decreased CYP1A1/2 mRNA expressions, EROD, and MROD activities in lungs, versus exposure to B(a)P alone. Nevertheless, exposure to B(a)P plus inhaled SO2 increased the mRNA and protein levels of c-jun and c-fos in lungs compared with lungs exposed to SO2 alone. Accordingly, the SO2-induced decreases of CYP1A1/2 might not influence the metabolic activation of B(a)P. However, when B(a)P and SO2 were given in the combinations, one might postulate that a synergistic effect on the expressions of c-fos and c-jun between SO2 and B(a)P, which might be one of the possible mechanisms of combination effects between B(a)P and the air pollutants.
二氧化硫（SO₂）是一种普遍存在的空气污染物，在城市空气中浓度较低，而在工作环境中浓度较高。苯并(a)芘（B(a)P）是一种多环芳烃，是一种普遍存在的环境污染物，具有多种毒理学效应。为了研究SO₂与B(a)P之间的相互作用，将雄性Wistar大鼠经气管内滴注苯并(a)芘（B(a)P；3毫克）或单独吸入SO₂（20 ppm）或两者同时暴露。分别使用实时逆转录-聚合酶链反应（实时RT-PCR）分析和蛋白质印迹分析来检测肺中CYP1A1和1A2、c-fos和c-jun的mRNA以及c-fos和c-jun的蛋白质水平。并检测了7-乙氧基异吩恶唑酮O-脱乙基酶（EROD）和甲氧基异吩恶唑酮O-脱甲基酶（MROD）的活性。在单独暴露于SO₂的大鼠肺中，CYP1A1和1A2的基因转录、EROD和MROD活性降低。同时，c-jun和c-fos的mRNA和蛋白质水平显著增加。单独暴露于B(a)P可诱导肺中CYP1A1、CYP1A2 mRNA水平、c-jun的蛋白质水平以及EROD和MROD活性。然而，与单独暴露于B(a)P相比，暴露于B(a)P加吸入SO₂既未增加也未降低肺中CYP1A1/2 mRNA表达、EROD和MROD活性。尽管如此，与单独暴露于SO₂的肺相比，暴露于B(a)P加吸入SO₂可增加肺中c-jun和c-fos的mRNA和蛋白质水平。因此，SO₂诱导的CYP1A1/2降低可能不会影响B(a)P的代谢活化。然而，当B(a)P和SO₂联合使用时，可以推测SO₂和B(a)P之间对c-fos和c-jun的表达具有协同作用，这可能是B(a)P与空气污染物联合效应的可能机制之一。
