The lack of apoptotic pathways may lead to undesirable cell survival and proliferation, which are recognized hallmarks of cancer. It is well known that exposure to cigarette smoke induces DNA lesions in pulmonary cells. At present, it is not fully elucidated whether these lesions are repaired to restore normal functions or induce apoptosis. In order to examine the role of apoptosis in smoking-induced effects, immortalized human bronchial epithelial cells (BEAS-2B) were exposed to cigarette smoke and examined for parameters associated with apoptosis and neoplastic transformation. Our results indicated a significant reduction in apoptosis and enhanced neoplastic transformation and decreased mitochondrial membrane potential Äøm of mitochondria compared to control cells. Time-course experiments revealed increased aberrant methylation of CpG islands of RAS-associated domain family protein 1A (RASSF1A) and O (6)-methylguanine-DNA-methyltransferase (MGMT). The activities were downregulated and repair of DNA adducts was inhibited. Our observations suggested that although cigarette smoke-induced damage in BEAS-2B cells after chronic exposure is not necessarily lethal, as evidenced by cell viability, the protein expression levels of caspase-3 showed a decrease in the S20 passage (metaphase) but subsequently increased from S30 to S40 (anaphase). Survivin expression was significantly changed in S5 cells, and this rise was maintained until S40. Our data suggest that the potency of cigarettes as carcinogens may be due to their ability to induce aberrant gene expression and failure to trigger apoptosis leads to subsequent neoplastic transformation.
Animals Apoptosis