Bhas 42 cell transformation activity of cigarette smoke condensate is modulated by selenium and arsenic

Cigarette smoking remains a major health risk worldwide. Development of newer tobacco products requires the use of quantitative toxicological assays. Recently, v-Ha-ras transfected BALB/c3T3 (Bhas 42) cell transformation assaywas established that simulates the two-stage animal tumorigenesis model and measures tumor initiatingand promoting activitiesof chemicals. The present study was performed to assess the feasibility of using this Bhas 42 cell transformation assayto determine the initiation and promotion activitiesof cigarette smoke condensate (CSC) and its water soluble fraction. Further, the modulating effects of selenium and arsenic on cigarette smoke-induced cell transformation were investigated. Dimethyl sulfoxide (DMSO) and water extracts of CSC (CSC-D and CSC-W, respectively) were tested at concentrations of 2.5–40 µg mL−1 in the initiation or promotion assayformats. Initiation protocol of the Bhas 42 assayshowed a 3.5-fold increase in transformed foci at 40 µg mL−1 of CSC-D but not CSC-W. The promotion phase of the assayyielded a robust dose response with CSC-D (2.5–40 µg mL−1) and CSC-W (20–40 µg mL−1). Preincubation of cells with selenium (100 nM) significantly reduced CSC-induced increase in cell transformation in initiation assay. Co-treatment of cells with a sub-toxic dose of arsenic significantly enhanced cell transformation activity of CSC-D in promotion assay. The results suggest a presence of both water soluble and insoluble tumor promotersin CSC, a role of oxidative stress in CSC-induced cell transformation, and usefulness of Bhas 42 cell transformation assayin comparing tobacco product toxicities and in studying the mechanisms of tobacco carcinogenesis. Environ. Mol. Mutagen., 2016. © 2016 Wiley Periodicals, Inc.