The expressions of protooncogenes and CYP1A in lungs of rats exposed to sulfur dioxide and benzo( a)pyrene

Abstract

Sulfur dioxide (SO 2) 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 SO 2 and B( a)P, male Wistar rats were exposed to intratracheally instilled with benzo( a)pyrene (B( a)P; 3 mg) or SO 2 (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 SO 2 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 SO 2 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 SO 2 increased the mRNA and protein levels of c-jun and c-fos in lungs compared with lungs exposed to SO 2 alone. Accordingly, the SO 2-induced decreases of CYP1A1/2 might not influence the metabolic activation of B( a)P. However, when B( a)P and SO 2 were given in the combinations, one might postulate that a synergistic effect on the expressions of c-fos and c-jun between SO 2 and B( a)P, which might be one of the possible mechanisms of combination effects between B( a)P and the air pollutants.