Epigenomic Effects of Hookah Tobacco Smoke in Human Respiratory Epithelia
Principal Investigator: David Schrump
Funding Mechanism: National Institutes of Health-Intramural
ID number: 252451
Award Date: 10/1/2012
Institution: National Cancer Institute (NCI)
The decreasing prevalence of cigarette smoking in the U.S. has coincided with the emergence of alternatives such as smoking flavored tobacco (shisha) via waterpipe (hookah). Although hookah smoke contains a number of carcinogens present in cigarette smoke, epidemiologic associations between hookah tobacco and lung cancer risk have not been firmly established, and the effects of hookah smoke on human respiratory epithelial cells have not been thoroughly investigated. The goal of this study is to determine whether, like cigarette smoke, hookah tobacco smoke will induce lung cancer-associated alterations in normal human respiratory epithelia in a time- and dose-dependent manner, and whether hookah smoke will increase stem cell signaling and enhance the malignant phenotype of human lung cancer cells. Study aims are: (1) to compare the effects of hookah tobacco and conventional cigarette smoke on DNA methylation, the histone code and global gene expression in cultured normal human respiratory epithelia and lung cancer cells; (2) to compare the effects of hookah tobacco and conventional cigarette smoke on microRNA expression in normal respiratory epithelia and lung cancer cells; (3) to compare the effects of hookah smoke and conventional cigarette smoke on stem cell gene expression in normal respiratory epithelia and lung cancer cells; and (4) to examine if hookah smoke enhances the malignant phenotype of lung cancer cells. Briefly, human small airway epithelial cells, human bronchial epithelial cells, and lung cancer cells derived from smokers and never-smokers will be cultured in the presence or absence of hookah or cigarette smoke condensates for up to 24 months. The investigators will perform various analyses and experiments to examine the effects of hookah smoke on DNA methylation, messenger RNA and microRNA profiles, and the histone code relative to the effects of conventional un-mentholated and mentholated cigarette smoke. They will also perform comparative genomic hybridization and DNA/RNA sequencing experiments to evaluate DNA mutations induced by hookah tobacco relative to conventional cigarette smoke. Additional experiments will determine if hookah smoke enhances the malignant phenotype of lung cancer cells. Results of these analyses will provide insights about hookah tobacco’s carcinogenic effects.