Effect of sulfur dioxide inhalation on CYP1A1 and CYP1A2 in rat liver and lung.
Sulfur dioxide (SO2) is a ubiquitous air pollutant, presents in low concentrations in the urban air, and in higher concentrations in the working environment. In the present study, male Wistar rats were housed in exposure chambers and treated with 14.00+/-1.53, 28.00+/-2.12 and 56.00+/-4.28 mg/m3 SO2 for 6 h/day for 7 days, while control rats were exposed to filtered air in the same condition. Highly specific substrates were used as probes of cytochrome P4501A1 (CYP1A1) and cytochrome P4501A2 (CYP1A2). The mRNA levels of CYP1A1 and 1A2 were analyzed in livers and lungs by using a real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) assay. Our results showed that the activities and mRNA levels of P450 were decreased in livers and lungs of rats exposed to SO2. In the liver, a decrease down to 0.68- and 0.64-fold in the CYP1A1 activity, probed by the O-deethylation of ethoxyresorufin (EROD), was observed at higher dose of SO2 (28 and 56 mg/m3); Similarly, CYP1A1 mRNA levels were reduced in livers of rats exposed to SO2 at 28 and 56 mg/m3. For livers, CYP1A2-mediated methoxyresorufin O-demethylase activity (MROD) was unaltered by SO2 at low concentrations, except for a significant decrease in the rats exposed to SO2 at 56 mg/m3 (0.79-fold); however, SO2 at higher concentrations significantly decreased levels of CYP1A2 (28 and 56 mg/m3) (p<0.05). Significant inhibition of both EROD and MROD was observed in lungs of rats exposed to SO2 at 28 and 56mg/m3. CYP1A1 activity was repressed 0.62- and 0.53-fold, while CYP1A2 activity was reduced to 0.74- and 0.55-fold in lungs, respectively. SO2 at higher concentrations (28 and 56 mg/m3) decreased significantly pulmonary CYP1A1 and 1A2 mRNA levels relative to control animals. Furthermore, the decreases of activities and mRNA levels of these P450 enzymes caused by SO2 at different concentrations in lungs and livers of rats followed linear dose-response curves. These results lead to the conclusion that SO2 exposure can reduce CYP1A1 and 1A2 in lungs and livers of rats and ROS and/or cytokines might act as mediators of this effect according to previous studies performed in mice. Reduction of hepatic and pulmonary CYPlAl and lA2 expression during SO2 exposure may be part of an adaptive response by the liver and lung to minimize cell damage.
Qin
Guohua
G
Institute of Environmental Medicine and Toxicology, Shanxi University, Taiyuan 030006, China.
Meng
Ziqiang
Z
D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism*; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D019570:Inhalation Exposure; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008168:Lung / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013458:Sulfur Dioxide / Q000633:toxicity*
D012333:RNA, Messenger; D013458:Sulfur Dioxide; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; C076307:methoxyresorufin-O-demethylase; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2