Effects of sulfur dioxide derivatives on expression of oncogenes and tumor suppressor genes in human bronchial epithelial cells

Sulfur dioxide (SO2) is a major air pollutant suspected to act as a promoter or co-carcinogen. The present study was designed to investigate whether SO2 derivatives (bisulfite and sulfite) had effects on the expression of several proto-oncogenes and tumor suppressor genes in cultured human bronchial epithelial (BEP2D) cells. The mRNA and protein levels were measured by real-time RT-PCR and western blotting, respectively, following exposure to differing SO2-derivative concentrations and exposure times. SO2 derivatives caused mRNA and protein over-expression of c-fos, c-jun, and c-myc at all tested doses (0.001-2 mM). Over-expression of H-ras and p53 were observed in cells receiving the highest concentration (0.1-2 mM), as well as the under-expression of p16 and Rb. The over-expression of c-fos and c-jun was observed after 24 h recovery. The expression of c-myc and H-ras decreased to base line levels while the p53 expression decreased compared with control after 24 h recovery. The mRNA and protein expression of p16 and Rb remained at initial levels after 24 h recovery. The data support the hypothesis that SO2 derivatives could cause the activation of proto-oncogenes and inactivation of tumor suppressor genes and SO2 derivatives may play a role in the pathogenesis of SO2-associated lung cancer.