Cigarette smoke-induced failure of apoptosis resulting in enhanced neoplastic transformation in human bronchial epithelial cells.

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 Δψm 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 adduct...