title: Cigarette smoke-induced failure of apoptosis resulting in enhanced neoplastic transformation in human bronchial epithelial cells.
abstract: 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 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.
authors: School of Public Health, Medical College of Soochow University, Suzhou, People's Republic of China.
authors: Houbing
authors: H
authors: Du
authors: Jing
authors: J
authors: Sun
authors: Zhihai
authors: Z
authors: Chen
authors: Jihua
authors: J
authors: Nie
authors: Jian
authors: J
authors: Tong
authors: Jianxiang
authors: J
authors: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001980:Bronchi / Q000166:cytology / Q000187:drug effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D019175:DNA Methylation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000139:chemically induced; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology*; D012907:Smoking / Q000009:adverse effects*
chemical_list: D012333:RNA, Messenger