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

• Published in: International journal of toxicology 2013-01, Vol.32 (1), p.23-31
• Main Authors: Word, Beverly, Lyn-Cook, Lascelles E., Mwamba, BiBi, Wang, Honggang, Lyn-Cook, Beverly, Hammons, George
• Format: Article
• Language: English
• Subjects: Apoptosis Regulatory Proteins - genetics; Biomarkers, Tumor - genetics; Cadherins - genetics; Calcium-Calmodulin-Dependent Protein Kinases - genetics; Cell Culture Techniques; Cell Line, Tumor; Data Interpretation, Statistical; Death-Associated Protein Kinases; DNA Methylation - genetics; DNA Modification Methylases - genetics; DNA Repair Enzymes - genetics; Dose-Response Relationship, Drug; Gene Expression; Humans; Lung Neoplasms - etiology; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Polymerase Chain Reaction; Promoter Regions, Genetic; Smoking - adverse effects; Tumor Suppressor Proteins - genetics
• ISSN: 1091-5818; 1092-874X
• DOI: 10.1177/1091581812465902

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.