Aberrant DNA methylation in radon and/or cigarette smoke-induced malignant transformation in BEAS-2B human lung cell line.

It is well known that cigarette smoking (CS) and/or radon (Rn) induce malignant transformation in lung cells. To investigate the mechanisms underlying lung carcinogenesis induced by CS, Rn; or Rn followed by CS using BEAS-2B cell line derived from human bronchial epithelial cells. BEAS-2B cells were exposed to either Rn (20,000 Bq/m3) for 30 min or CS (20%) for 10 min or Rn followed by CS for 40 min. Global and gene-specific DNA methylation modifications were measured by microarray and methylation-specific polymerase chain reaction. Cell cycle and apoptosis were determined by flow cytometry, while soft agar colony formation was conducted to assess the characteristics of malignant transformation. Data demonstrated global hypomethylation as well as gene-specific DNA methylation alterations in all treatment groups compared to unexposed control cells. In addition, Rn and CS produced DNA hypermethylation of protein tyrosine phosphatase receptor type M and ectodysplasin A2 receptor, two genes related to malignant transformation. In all treatment conditions, cell proliferation and survival of malignant cells was increased, while apoptosis was initially first passage elevated but decreased at passages 5-15. Our results indicate that aberrant DNA methylation plays an important role in Rn- and/or CS-induced malignant transformation. In addition, BEAS-2B cell line may be used as an in vitro model to investigate mechanisms underlying malignant transformation induced by ambient environmental contaminants.