Expression of oncogenes and tumor suppressor genes in lungs of rats exposed to sulfur dioxide and benzo(a)pyrene

Author: Qin Guohua   Meng Ziqiang  

Publisher: Informa Healthcare

ISSN: 1091-7691

Source: Inhalation Toxicology, Vol.22, Iss.4, 2010-03, pp. : 322-329

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Abstract

Concurrent exposure to SO2 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 SO2 and B(a)P was observed in lungs after SO2 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 SO2 and B(a)P, male Wistar rats were exposed via intratracheal instillation of B(a)P (3 mg) or SO2 (56 mg/m3) 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 SO2 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 SO2 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 SO2 and B(a)P exposure may be critical to understanding the mechanisms of SO2 cocarcinogenesis and helpful for therapeutic intervention.