Cell transformation assays have been commonly used to predict chemical carcinogenicity. Using v-Ha-ras transfected BALB/c3T3 (Bhas 42) cells, Sasaki and coworkers (2010, 2011) have recently validated a sensitive short-term assay that simulates the two-stage animal tumorigenesis model and measures tumor initiating and promoting activities of chemicals. In the present study, we used this assay to determine the cell transformation activity of cigarette smoke condensate (CSC) in Bhas 42 cells. DMSO and water extracts of CSC (CSC-D & CSC-W, respectively) from the University of Kentucky reference cigarettes were prepared and tested at concentrations of 2.5 µg to 40 µg/ml in the initiator or promoter assay formats. The results of the initiator assay showed up to 3.5- fold increase in transformed foci at 40 µg/ml of CSC-D but none by CSC-W. In contrast, a robust dose response (up to 14-fold increase) was observed in the promoter assay between 5 µg to 40 µg/ml of CSC-D and 20 µg to 40 µg/ml of CSC-W. Pre- and co-incubation of Bhas 42 cells with selenium (100nM) significantly reduced CSC activity in initiator assay suggesting a role of oxidative stress in CSC-induced cell transformation. Co-treatment of cells with a sub-toxic dose of arsenate significantly enhanced cell transformation activity of CSC-D in promoter assay suggesting a synergistic interaction. The results suggest i) the presence of both water soluble and insoluble tumor promoters in CSC, ii) a role of oxidative stress in CSC-induced cell transformation, iii) a potential interaction of smoking with environmental metal pollutants in influencing neoplastic changes, and iv) a potential for application of Bhas 42 assay in initiator/promoter activity assessment of CSCs from different cigarettes.