Thirdhand smoke causes DNA damage in human cells

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.

The Challenges of Limiting Exposure to THS in Vulnerable Populations

“…Not surprisingly, given its composition, THS has been shown to damage DNA. An in vitro system with human HepG2 cells and THS, generated both acutely and chronically, showed significant DNA strand breaks compared to controls [10]. The exposure to chronic THS resulted in more DNA damage than the acutely generated exposure material [10].…”

Environmental Damages of Tobacco: Only Human Being Damage?

“…Bu çalışmadaki veriler çevreyle ve tozla teması normal bireylere göre çok daha fazla olan bebekler ve çocuklar için THS'e maruziyetin daha riskli olduğunu desteklemesi açısından önemlidir. Güncel bir çalışma THS maruziyetinin insan hücrelerinde genotoksik olduğunu bildirmiştir (15) . Çalışmada yü-zeyde kalan nikotinin atmosferik nitrojen oksidlerle (HONO) reaksiyonu sonucu açığa çıkan tütün spesifik karsinojenik nitrozaminlerin (TSNA) DNA hasarlanmasına yol açtığı gösterilmiştir.…”

Thirdhand smoke: when the danger is more than you can see or smell

“…Half of the nicotine deposited on clothing and dissolved by sweat can penetrate the body through the skin and be absorbed 71 . There is no clear linear relationship between the exposure dose to THS and harmful effects 72,73 .…”

“…Meanwhile the genotoxic effect was observed in human hepatocellular carcinoma cells (HepG-2) exposed to THS, resulting in increased DNA strand breaks using the comet assay 72 . Murine neural stem cells (mNSC) and human dermal fibroblasts (hDF) were exposed to a culture medium prepared with fabric material present inside automobiles from which THS was collected and evaluated with the comet assay.…”

“…Cells treated with this material showed a higher percentage with migration of chromosomal DNA and longer tails 62 . Chronic exposure to THS resulted in oxidative DNA damage in genes involved in nucleotide metabolism and repair mechanism in human bronchial epithelial cells (BEAS-2B) 72 . In addition, together with NNK, NNA can induce base mutation in DNA and result in uncontrolled cell growth and thus tumor formation 35 .…”