title: Extracts from presumed "reduced harm" cigarettes induce equivalent or greater toxicity in antigen-presenting cells.
abstract: The tobacco industry has promoted certain cigarette products with claims that their use may be less harmful to the smoker as they purportedly deliver lower amounts of toxic chemicals compared to conventional cigarettes. This study was designed to compare the relative antigen presenting cellular toxicity of Eclipse, a presumed reduced exposure product (PREP) cigarette, when compared with the reference research 3R4F cigarettes (Kentucky University). Utilizing a murine macrophage cell line, murine bone marrow derived dendritic cells (DCs) and human monocyte-derived DCs incubated with extracts generated from Eclipse and Kentucky reference 3R4F cigarettes, we determined the relative toxic effects of the different cigarette smoke extracts on cellular viability, oxidative stress, T-helper-1 (Th-1) polarizing cytokine production and general gene expression. Eclipse and 3R4F cigarette smoke extracts induced equivalent oxidatively-mediated cellular heme oxygenase-1 (HO-1) protein levels in macrophages and DCs. Cellular viability determination demonstrated greater induction of cell death by apoptosis and necrosis by Eclipse extracts in DCs. The production of the key Th-1 polarizing cytokine interleukin-12 (IL-12) by activated DCs or macrophages was suppressed to an equivalent or greater extent by Eclipse extracts. Microarray studies performed on bone marrow derived murine DCs incubated with Eclispe or 3R4F cigarette extracts showed identical genotoxic profiles. These studies imply that presumed reduced harm Eclipse cigarettes induce equivalent or greater antigen presenting cell dysfunction relative to 3R4F cigarettes and illustrate the importance of independent validation and testing of similar products claimed to be associated with reduced toxicity relative to other cigarettes.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, USA; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: Vassallo.Robert@mayo.edu.
authors.forename: Robert
authors.initials: R
authors.lastname: Vassallo
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: Rudu0226@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: Kopanda75kishou1851@yahoo.co.jp.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Hirano
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: Walters.Paula@mayo.edu.
authors.forename: Paula
authors.initials: P
authors.lastname: Walters
authors.affiliation: Division of Biomedical Statistics and Informatics, Health Sciences Research, Mayo Clinic, Rochester, MN, USA. Electronic address: Grill.Diane@mayo.edu.
authors.forename: Diane
authors.initials: D
authors.lastname: Grill
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D018570:Risk Assessment; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D062789:Tobacco Products / Q000633:toxicity*; D018675:Toxicity Tests
chemical_list: D016207:Cytokines; D008565:Membrane Proteins; D012906:Smoke; D018664:Interleukin-12; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: Antigen presenting cell; Cigarette smoke extract; Dendritic cell; Eclipse; Gene array