Expression of oncogenes and tumor suppressor genes in lungs of rats exposed to sulfur dioxide and benzo(a)pyrene.
Concurrent exposure to SO(2) and benzo(a)pyrene (B(a)P) resulted in an increased incidence of lung tumors in rodents compared to exposure to B(a)P alone. A synergistic effect on the expression of c-fos and c-jun between SO(2) and B(a)P was observed in lungs after SO(2) and B(a)P exposure. However, tumorigenesis occurs by multiple events that may involve the activation of more than one oncogene, as well as the functional loss of the tumor suppressor gene. In order to further investigate the interactions between SO(2) and B(a)P, male Wistar rats were exposed via intratracheal instillation of B(a)P (3 mg) or SO(2) (56 mg/m(3)) inhalation, alone or together. The mRNA and protein levels of oncogenes (c-myc and H-ras) and tumor suppressor genes (p53, p16, and Rb) were analyzed in lungs by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot, respectively. The results showed that all treatments increased mRNA and protein expression levels of c-myc, H-ras, and p53, and reduced expression levels of p16 and Rb. In general, the combination of SO(2) and B(a)P was more effective in influencing these expression levels than either agent alone, except for H-ras expression. These findings indicate that multiple cell cycle regulatory proteins play key roles in the toxicity of SO(2) and B(a)P. It might involve the activation of c-fos, c-jun, c-myc, and p53. And the p16-Rb pathway might also participate in the progress. Elucidating the expression patterns of those factors after SO(2) and B(a)P exposure may be critical to understanding the mechanisms of SO(2) cocarcinogenesis and helpful for therapeutic intervention.
Qin
Guohua
G
Institute of Environmental Medicine and Toxicology, Research Center of Environmental Science and Engineering, Shanxi University, Taiyuan, China.
Meng
Ziqiang
Z
D000280:Administration, Inhalation; D000818:Animals; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000633:toxicity*; D015153:Blotting, Western; D018076:DNA, Complementary / Q000096:biosynthesis / Q000302:isolation & purification; D004785:Environmental Pollutants / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects*; D016161:Genes, Retinoblastoma / Q000187:drug effects; D016147:Genes, Tumor Suppressor / Q000187:drug effects*; D019942:Genes, p16 / Q000187:drug effects; D016158:Genes, p53 / Q000187:drug effects; D011905:Genes, ras / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D009857:Oncogenes / Q000235:genetics*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013458:Sulfur Dioxide / Q000008:administration & dosage / Q000633:toxicity*
D018076:DNA, Complementary; D004785:Environmental Pollutants; D013458:Sulfur Dioxide; D001564:Benzo(a)pyrene; D012313:RNA