Cited by 171Carcinogens and Genotoxicity AssessmentSmoking Behavior and CessationDNA Repair Mechanisms

Thirdhand smoke causes DNA damage in human cells

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Hang, B., Sarker, A. H., Havel, C., Saha, S., Hazra, T. K., Schick, S., Jacob, P., Rehan, V. K. +5 more·2013·Mutagenesis

Abstract

Exposure to thirdhand smoke (THS) is a newly described health risk. Evidence supports its widespread presence in indoor environments. However, its genotoxic potential, a critical aspect in risk assessment, is virtually untested. An important characteristic of THS is its ability to undergo chemical transformations during aging periods, as demonstrated in a recent study showing that sorbed nicotine reacts with the indoor pollutant nitrous acid (HONO) to form tobacco-specific nitrosamines (TSNAs) such as 4-(methylnitrosamino)-4-(3-pyridyl)butanal (NNA) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The goal of this study was to assess the genotoxicity of THS in human cell lines using two in vitro assays. THS was generated in laboratory systems that simulated short (acute)- and long (chronic)-term exposures. Analysis by liquid chromatography-tandem mass spectrometry quantified TSNAs and common tobacco alkaloids in extracts of THS that had sorbed onto cellulose substrates. Exposure of human HepG2 cells to either acute or chronic THS for 24h resulted in significant increases in DNA strand breaks in the alkaline Comet assay. Cell cultures exposed to NNA alone showed significantly higher levels of DNA damage in the same assay. NNA is absent in freshly emitted secondhand smoke, but it is the main TSNA formed in THS when nicotine reacts with HONO long after smoking takes place. The long amplicon-quantitative PCR assay quantified significantly higher levels of oxidative DNA damage in hypoxanthine phosphoribosyltransferase 1 (HPRT) and polymerase β (POLB) genes of cultured human cells exposed to chronic THS for 24h compared with untreated cells, suggesting that THS exposure is related to increased oxidative stress and could be an important contributing factor in THS-mediated toxicity. The findings of this study demonstrate for the first time that exposure to THS is genotoxic in human cell lines.

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Crossref · 10.1093/mutage/get013

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  • Cells in the skin of THS-exposed mice are under significant stress from smoke toxicants.

    “In particular, the DNA damage observed in the skin of the THS-exposed mice was very high suggesting that the cells are under significant stress from the smoke toxicants [18].”

    From Tobacco toxins deposited on surfaces (third hand smoke) impair wound healing (2016) · cites this paper as [18]

    The Comet assay results report significantly greater DNA damage after THS exposure, and the Discussion links THS to oxidative DNA damage. Those findings concern cultured human cells, not skin cells from THS-exposed mice; the source does not establish the claimed stress in mouse skin. (LLM, conf=0.86)

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  • DNA damage observed in the skin of THS-exposed mice was very high.

    “In particular, the DNA damage observed in the skin of the THS-exposed mice was very high suggesting that the cells are under significant stress from the smoke toxicants [18].”

    From Tobacco toxins deposited on surfaces (third hand smoke) impair wound healing (2016) · cites this paper as [18]

    The section ‘THS leads to accumulation of oxidative DNA damage in the LA-QPCR assay’ reports a high level of DNA damage in THS-exposed human lung epithelial cells. The cited paper does not report DNA damage in the skin of THS-exposed mice, so it does not support that species- and tissue-specific observation. The indexed passages provide no page number. (LLM, conf=0.86)

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Authors
Hang, B., Sarker, A. H., Havel, C., Saha, S., Hazra, T. K., Schick, S., Jacob, P., Rehan, V. K., Chenna, A., Sharan, D., Sleiman, M., Destaillats, H., & Gundel, L. A.
Affiliations
  • Lawrence Berkeley National Laboratory (US)
  • San Francisco General Hospital (US)
  • The University of Texas Medical Branch at Galveston (US)
  • University of California, Los Angeles (US)
Corresponding author
Hang, B.
Venue
Mutagenesis
Published
2013-03-05
Volume
28
Issue
4
Pages
381-391
ISSN
  • 0267-8357 (ISSN-L)
  • 1464-3804
OpenAlex
W2189202059
Cited by
171
References
50
Citations by year
2026: 13 · 2025: 13 · 2024: 12 · 2023: 13 · 2022: 12 · 2021: 11 · 2020: 15 · 2019: 14 · 2018: 12 · 2017: 11 · 2016: 15 · 2015: 16 · 2014: 10 · 2013: 4
FWCI
5.28
Type
journal article
Language
en
Open access
Locations
  • Mutagenesis (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Energy (19XT-0070)
  • Tobacco-Related Disease Research Program (20PT-0184, 19XT-0070)
  • National Institutes of Health (UL1TR000124)
  • National Institute on Drug Abuse (P30DA012393)
  • National Center for Research Resources (S10RR026437)
  • National Center for Advancing Translational Sciences
  • Lawrence Berkeley National Laboratory
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Keywords
thirdhand smoke, genotoxicity, DNA damage, tobacco-specific nitrosamines, NNK, nitrous acid, nicotine, oxidative DNA damage, oxidative stress, HepG2 cells, indoor air pollution, tobacco alkaloids, HPRT, POLB
MeSH terms
Cell Line, DNA Damage, Humans, Mutagens, Nitrous Acid, Tobacco Smoke Pollution, Oxidative Stress, Comet Assay, DNA Breaks

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