title: Cigarette smoke condensate induces differential expression and promoter methylation profiles of critical genes involved in lung cancer in NL-20 lung cells in vitro: short-term and chronic exposure.
abstract: Establishing early diagnostic markers of harm is critical for effective                      prevention programs and regulation of tobacco products. This study examined                      effects of cigarette smoke condensate (CSC) on expression and promoter                      methylation profile of critical genes (DAPK, ECAD, MGMT, and RASSF1A) involved                      in lung cancer development in different human lung cell lines. NL-20 cells were                      treated with 0.1-100 μg/ml of CSC for 24 to 72 hrs for short-term exposures.                      DAPK expression or methylation status was not significantly affected. However,                      CSC treatment resulted in changes in expression and promoter methylation profile                      of ECAD, MGMT, and RASSF1A. For chronic studies, cells were exposed to 1 or 10                      μg/ml CSC up to 28 days. Cells showed morphological changes associated with                      transformation and changes in invasion capacities and global methylation status.                      This study provides critical data suggesting that epigenetic changes could serve                      as an early biomarker of harm due to exposure to cigarette smoke.
authors.affiliation: HFT-100, Office of Regulatory Activities, National Center for Toxicological Research, Jefferson, AR 72079, USA.
authors.forename: Beverly
authors.initials: B
authors.lastname: Word
authors.forename: Lascelles E
authors.initials: LE
authors.lastname: Lyn-Cook
authors.forename: Bibi
authors.initials: B
authors.lastname: Mwamba
authors.forename: Honggang
authors.initials: H
authors.lastname: Wang
authors.forename: Beverly
authors.initials: B
authors.lastname: Lyn-Cook
authors.forename: George
authors.initials: G
authors.lastname: Hammons
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics*; D015820:Cadherins / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000235:genetics*; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D003627:Data Interpretation, Statistical; D064550:Death-Associated Protein Kinases; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012907:Smoking / Q000009:adverse effects*; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; D015820:Cadherins; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D045643:DNA Repair Enzymes