PMID- 26719373 OWN - NLM STAT- MEDLINE DCOM- 20161213 LR - 20180501 IS - 1096-0929 (Electronic) IS - 1096-0929 (Linking) VI - 150 IP - 1 DP - 2016 Mar TI - Cytotoxicity of Thirdhand Smoke and Identification of Acrolein as a Volatile Thirdhand Smoke Chemical That Inhibits Cell Proliferation. PG - 234-46 LID - 10.1093/toxsci/kfv327 [doi] AB - 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. CI - (c) The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. FAU - Bahl, Vasundhra AU - Bahl V AD - *Department of Cell Biology and Neuroscience, University of California, Riverside, California 92521, USA; Environmental Toxicology Graduate Program; FAU - Weng, Nikki J-H AU - Weng NJ AD - *Department of Cell Biology and Neuroscience, University of California, Riverside, California 92521, USA; Cell Molecular and Developmental Biology Graduate Program; FAU - Schick, Suzaynn F AU - Schick SF AD - Division of Occupational and Environmental Medicine, Department of Medicine, University of California, San Francisco, California 94243, USA; FAU - Sleiman, Mohamad AU - Sleiman M AD - Lawrence Berkley National Laboratory, Berkeley, California 94720, USA; and. FAU - Whitehead, Jacklyn AU - Whitehead J AD - *Department of Cell Biology and Neuroscience, University of California, Riverside, California 92521, USA; Bioengineering Interdepartmental Graduate Program. FAU - Ibarra, Allison AU - Ibarra A AD - *Department of Cell Biology and Neuroscience, University of California, Riverside, California 92521, USA; FAU - Talbot, Prue AU - Talbot P AD - *Department of Cell Biology and Neuroscience, University of California, Riverside, California 92521, USA; prue.talbot@ucr.edu. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20151229 PL - United States TA - Toxicol Sci JT - Toxicological sciences : an official journal of the Society of Toxicology JID - 9805461 RN - 0 (Tetrazolium Salts) RN - 0 (Thiazoles) RN - 0 (Tobacco Smoke Pollution) RN - 0 (Volatile Organic Compounds) RN - 7864XYD3JJ (Acrolein) RN - EUY85H477I (thiazolyl blue) SB - IM MH - A549 Cells MH - Acrolein/chemistry/*toxicity MH - Animals MH - Cell Cycle/drug effects/genetics MH - Cell Proliferation/*drug effects/genetics MH - Cell Survival/drug effects/genetics MH - Fibroblasts/*drug effects/pathology MH - Humans MH - Mice MH - Neural Stem Cells/*drug effects/pathology MH - Tetrazolium Salts/chemistry MH - Thiazoles/chemistry MH - Tobacco Smoke Pollution/*adverse effects/analysis MH - Volatile Organic Compounds/chemistry/*toxicity OTO - NOTNLM OT - THS OT - acrolein OT - cell cycle OT - cell proliferation OT - cytotoxicity OT - lung cells OT - stem cells OT - thirdhand smoke OT - volatile organic chemicals EDAT- 2016/01/01 06:00 MHDA- 2016/12/15 06:00 CRDT- 2016/01/01 06:00 PHST- 2016/01/01 06:00 [entrez] PHST- 2016/01/01 06:00 [pubmed] PHST- 2016/12/15 06:00 [medline] AID - kfv327 [pii] AID - 10.1093/toxsci/kfv327 [doi] PST - ppublish SO - Toxicol Sci. 2016 Mar;150(1):234-46. doi: 10.1093/toxsci/kfv327. Epub 2015 Dec 29.