Secondhand smoke induces liver steatosis through deregulation of genes involved in lipid metabolism.
Ontology highlight
ABSTRACT: In this study, we have investigated the role of secondhand smoke (SHS) in the development of metabolic liver disease by characterizing the global regulation of genes and molecular pathways in SHS-exposed mice after termination of exposure (SHS 4M) and following one-month recovery in clean air (SHS 4M +1M RECOVERY).
Project description:A large body of evidence has linked secondhand smoke (SHS) to lung cancer in nonsmokers. Yet, the underlying mechanisms of SHS carcinogenicity in nonsmokers' lung cancer remain elusive. Recently, we have demonstrated a genotoxic mode of action for SHS, based on the ability of this carcinogen to induce adduct-driven mutagenesis in transgenic Big Blue® mice. In the present study, we have expanded this investigation to determine whether SHS can also cause epigenetic effects through aberrations of DNA methylation. Here, we have globally profiled DNA methylation in the lung of Big Blue® mice exposed to SHS for a duration of 4-months, both immediately after the termination of exposure and at several intervals post-exposure. We have used a genome-wide microarray-based approach to catalogue DNA methylation profile in the lung of mice exposed to SHS and at various recovery periods from the time of exposure. Mice exposed to clean air, for comparable amount of times, were used as controls. Mice that were injected intraperitoneally with chronic doses of B(a)P (a powerful carcinogen in SHS) or DMSO (sham) were used for comparison purposes .
Project description:Second-hand smoke (SHS) exposure during pregnancy has adverse effects on offspring. We used microarrays to characterize the gene expression changes caused by in-utero exposure and adult exposure to SHS in adult mouse lungs. Left lungs from Balb/c male mice were collected at 15 weeks of age for RNA extraction and hybridization on Affymetrix mouse 430 2.0 microarrays. Based on their smoke exposure status, there are 4 groups of mice, each exposed in-utero to filtered-air or SHS and as an adult to filtered-air or SHS. We extracted RNA from 4 animals from each group for microarray analysis (N = 16 samples).
Project description:Second-hand smoke (SHS) exposure during pregnancy has adverse effects on offspring. We used microarrays to characterize the gene expression changes caused by in-utero exposure and adult exposure to SHS in adult mouse lungs.
Project description:A large body of evidence has linked secondhand smoke (SHS) to lung cancer in nonsmokers. Yet, the underlying mechanisms of SHS carcinogenicity in nonsmokers' lung cancer remain elusive. Recently, we have demonstrated a genotoxic mode of action for SHS, based on the ability of this carcinogen to induce adduct-driven mutagenesis in transgenic Big Blue® mice. In the present study, we have expanded this investigation to determine whether SHS can also cause epigenetic effects through aberrations of DNA methylation. Here, we have globally profiled DNA methylation in the lung of Big Blue® mice exposed to SHS for a duration of 4-months, both immediately after the termination of exposure and at several intervals post-exposure.
Project description:Our previous studies have shown that tobacco smoke exposure exacerbated the lung response to crystalline silica exposure in rats. The objective of the present study, a follow-up to our previous study, was to determine the effect of tobacco smoke exposure cessation on the lung response to crystalline silica exposure in the rats. Rats were exposed to air, crystalline silica (1 week followed by a 1 year progression/recovery period with no exposure), tobacco smoke (6 months of exposure followed by 6 months of recovery with no exposure), or crystalline silica (1 week) plus tobacco smoke (6 months of exposure followed by 6 months of recovery with no exposure). Lung toxicity was determined at the end of the 1-year progression/recovery period in all 4 groups of the rats. Silica exposure resulted in significant lung toxicity which was further exacerbated by tobacco smoke exposure in the rats. Cessation of cigarette smoke exposure did not result in reversal of the silica-induced lung toxicity despite exacerbation of the toxicity by tobacco smoke.
Project description:normal human bronchial epithelial cultures from two cultures in parallel exposed to cigarette smoke (CS) or air (mock) at timepoints 4 hours and 24 hours. Keywords = cigarette smoke Keywords = microarray Keywords = bronchial cell Keywords = tobacco Keywords: time-course
Project description:Cell cultures from three human non-smoker donors were exposed 1:50 dose (1.84ug/cm2) of diluted mainstream cigarette smoke or filtered air for 1h. Cells from four replicate inserts for each dose/time-point were pooled and placed in TRIzol either immediately after exposure or following a 5h or 23h recovery period after the cultures were returned to an incubator at 37ºC, 5% CO2. The ‘no treatment’ control (NTC) remained in the incubator and received neither smoke nor air. In order to perform robust statistical analyses three independent replicate experiments were performed on each of the three donors
Project description:To investigate the effect of cigarette smoke exposure on gene expression in airway epithelial cells of Canton S Drosophila melanogaster larvae, we isolated the airways of cigarette smoke exposed larvae and air controls. We then performed gene expression profiling analysis using data obtained from RNA-seq of smoke-exposed males, smoke-exposed females, air-control males and air-control females. For each group 4 biological replicates were prepared, representing 40-50 larval airways.
Project description:The aim of this study was to develop human bronchial and nasal epithelium culture models that are relevant to investigate the impact of cigarette smoke (CS) observed in vivo in respiratory tract tissues in contact with inhaled CS. We used two organotypic cultures generated from primary cells derived from non-smoking donors that contain fibroblasts and epithelial cells in order to reproduce as closely as possible the in vivo situation. To mimic the smoking behavior of a moderate smoker during one day, human tissue cultures (bronchial and nasal epithelium) were exposed repeatedly and directly at the air/liquid interface (using the Vitrocell(R) System) to two doses (high 4.2 ug TPM/cm2 and low 2.2 ug TPM/cm2 per cigarette) of the whole smoke generated by one cigarette or to humidified air (sham). CS exposure was repeated four times with one hour intervals between each cigarette. Various endpoints (e.g., gene and microRNA expression, CYP activity, pro-inflammatory markers release, differential cell counts, cytotoxicity measurement) were then captured to assess the baseline (time 0) and early responses of the tissues after exposure (4 hours) as well as the recovery phase (24 and 48 hours).