Cytotoxicity of Thirdhand Smoke and Identification of Acrolein as a Volatile Thirdhand Smoke Chemical That Inhibits Cell Proliferation
| Autor: | Prue Talbot, Allison Ibarra, Jacklyn Whitehead, Nikki Jo-Hao Weng, Suzaynn F. Schick, Mohamad Sleiman, Vasundhra Bahl |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
thirdhand smoke Cell Survival Tetrazolium Salts 010501 environmental sciences Toxicology 01 natural sciences 03 medical and health sciences chemistry.chemical_compound Mice THS Neural Stem Cells stem cells Cytotoxic T cell Organic chemistry Animals Humans Acrolein Cytotoxicity Mode of action Lung 0105 earth and related environmental sciences Cell Proliferation Volatile Organic Compounds lung cells Chemistry Cell growth Cell Cycle volatile organic chemicals Pharmacology and Pharmaceutical Sciences Cell cycle Fibroblasts Molecular biology Thiazoles 030104 developmental biology Vacuolization A549 Cells Toxicity cytotoxicity Tobacco Smoke Pollution |
| Zdroj: | Toxicological sciences : an official journal of the Society of Toxicology, vol 150, iss 1 Bahl, V; Weng, NJ-H; Schick, SF; Sleiman, M; Whitehead, J; Ibarra, A; et al.(2016). Cytotoxicity of Thirdhand Smoke and Identification of Acrolein as a Volatile Thirdhand Smoke Chemical That Inhibits Cell Proliferation. TOXICOLOGICAL SCIENCES, 150(1), 234-246. doi: 10.1093/toxsci/kfv327. UC Riverside: Retrieved from: http://www.escholarship.org/uc/item/4k69r4fr |
| DOI: | 10.1093/toxsci/kfv327. |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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