title: Cytotoxicity of Thirdhand Smoke and Identification of Acrolein as a Volatile Thirdhand Smoke Chemical That Inhibits Cell Proliferation.
abstract: Thirdhand smoke (THS) is a mixture of chemicals that remain on indoor surfaces after smoking has ceased. These chemicals can be inhaled, ingested, or absorbed dermally, and thus could impact human health. We evaluated the cytotoxicity and mode of action of fresh and aged THS, the toxicity of volatile organic chemicals (VOCs) in THS, and the molecular targets of acrolein, a VOC in THS. Experiments were done using mouse neural stem cells (mNSC), human pulmonary fibroblasts (hPF), and lung A549 epithelial cells. THS-exposed cotton cloth was extracted in Dulbecco's Eagle Medium and caused cytotoxicity in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. THS extracts induced blebbing, immotility, vacuolization, cell fragmentation, severing of microfilaments and depolymerization of microtubules in mNSC. Cytotoxicity was inversely related to headspace volume in the extraction container and was lost upon aging, suggesting that VOCs in THS were cytotoxic. Phenol, 2',5'-dimethyl furan and acrolein were identified as the most cytotoxic VOCs in THS, and in combination, their cytotoxicity increased. Acrolein inhibited proliferation of mNSC and hPF and altered expression of cell cycle regulatory genes. Twenty-four hours of treatment with acrolein decreased expression of transcription factor Dp-1, a factor needed for the G1 to S transition in the cell cycle. At 48 h, WEE1 expression increased, while ANACP1 expression decreased consistent with blocking entry into and completion of the M phase of the cell cycle. This study identified acrolein as a highly cytotoxic VOC in THS which killed cells at high doses and inhibited cell proliferation at low doses.
authors.affiliation: *Department of Cell Biology and Neuroscience, University of California, Riverside, California 92521, USA; Environmental Toxicology Graduate Program;
authors.forename: Vasundhra
authors.initials: V
authors.lastname: Bahl
authors.affiliation: *Department of Cell Biology and Neuroscience, University of California, Riverside, California 92521, USA; Cell Molecular and Developmental Biology Graduate Program;
authors.forename: Nikki J-H
authors.initials: NJ
authors.lastname: Weng
authors.affiliation: Division of Occupational and Environmental Medicine, Department of Medicine, University of California, San Francisco, California 94243, USA;
authors.forename: Suzaynn F
authors.initials: SF
authors.lastname: Schick
authors.affiliation: Lawrence Berkley National Laboratory, Berkeley, California 94720, USA; and.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Sleiman
authors.affiliation: *Department of Cell Biology and Neuroscience, University of California, Riverside, California 92521, USA; Bioengineering Interdepartmental Graduate Program.
authors.forename: Jacklyn
authors.initials: J
authors.lastname: Whitehead
authors.affiliation: *Department of Cell Biology and Neuroscience, University of California, Riverside, California 92521, USA;
authors.forename: Allison
authors.initials: A
authors.lastname: Ibarra
authors.affiliation: *Department of Cell Biology and Neuroscience, University of California, Riverside, California 92521, USA; prue.talbot@ucr.edu.
authors.forename: Prue
authors.initials: P
authors.lastname: Talbot
mesh_terms: D000072283:A549 Cells; D000171:Acrolein / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects* / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D051379:Mice; D058953:Neural Stem Cells / Q000187:drug effects* / Q000473:pathology; D013778:Tetrazolium Salts / Q000737:chemistry; D013844:Thiazoles / Q000737:chemistry; D014028:Tobacco Smoke Pollution / Q000009:adverse effects* / Q000032:analysis; D055549:Volatile Organic Compounds / Q000737:chemistry / Q000633:toxicity*
chemical_list: D013778:Tetrazolium Salts; D013844:Thiazoles; D014028:Tobacco Smoke Pollution; D055549:Volatile Organic Compounds; D000171:Acrolein; C022616:thiazolyl blue
keywords: THS; acrolein; cell cycle; cell proliferation; cytotoxicity; lung cells; stem cells; thirdhand smoke; volatile organic chemicals