Abstract
No previous studies have shown that acute inhalation of thirdhand smoke (THS) activates stress and survival pathways in the human nasal epithelium. To evaluate gene expression in the nasal epithelium of nonsmoking women following acute inhalation of clean air and THS. Nasal epithelium samples were obtained from participants in a randomized clinical trial (2011-2015) on the health effects of inhaled THS. In a crossover design, participants were exposed, head only, to THS and to conditioned, filtered air in a laboratory setting. The order of exposures was randomized and exposures were separated by at least 21 days. Ribonucleic acid was obtained from a subset of 4 healthy, nonsmoking women. By chance, women in the subset were randomized to receive clean air exposure first and THS exposure second. Exposures lasted 3 hours. Differentially expressed genes were identified using RNA sequencing with a false-discovery rate less than 0.1. Participants were 4 healthy, nonsmoking women aged 27 to 49 years (mean [SD] age, 42 [10.2] years) with no chronic diseases. A total of 389 differentially expressed genes were identified in nasal epithelium exposed to THS, while only 2 genes, which were not studied further, were affected by clean air. Enriched gene ontology terms associated with stress-induced mitochondrial hyperfusion were identified, such as respiratory electron transport chain (q = 2.84 × 10-3) and mitochondrial inner membrane (q = 7.21 × 10-6). Reactome pathway analysis identified terms associated with upregulation of DNA repair mechanisms, such as nucleotide excision repair (q = 1.05 × 10-2). Enrichment analyses using ingenuity pathway analysis identified canonical pathways related to stress-induced mitochondrial hyperfusion (eg, increased oxidative phosphorylation) (P = .001), oxidative stress (eg, glutathione depletion phase II reactions) (P = .04), and cell survival (z score = 5.026). This study found that acute inhalation of THS caused cell stress that led to the activation of survival pathways. Some responses were consistent with stress-induced mitochondrial hyperfusion and similar to those demonstrated previously in vitro. These data may be valuable to physicians treating patients exposed to THS and may aid in formulating regulations for the remediation of THS-contaminated environments.
Highlights
Thirdhand smoke (THS) is a subset of chemicals in secondhand cigarette smoke that sticks to indoor surfaces and persists after active smoking has occurred.[1,2] Chemicals in THS accumulate and can react with other compounds or can be reemitted into the environment.[1,2,3] Nonsmokers can be exposed to chemicals in THS months or even years after smoking has stopped.[3]
This study found that acute inhalation of THS caused cell stress that led to the activation of survival pathways
The data set consisted of approximately 10 000 genes, of which 2 and 389 were significantly differentially affected (FDR
Summary
Thirdhand smoke (THS) is a subset of chemicals in secondhand cigarette smoke (sidestream smoke emitted by a burning cigarette and exhaled mainstream smoke) that sticks to indoor surfaces and persists after active smoking has occurred.[1,2] Chemicals in THS accumulate and can react with other compounds or can be reemitted into the environment.[1,2,3] Nonsmokers can be exposed to chemicals in THS months or even years after smoking has stopped.[3] Many THS chemicals are toxic volatile and semivolatile organic compounds.[2,3,4] Nicotine, a major chemical in THS, has a high affinity for surfaces[3] and can react with ambient nitrous acid to form tobacco-specific nitrosamines, some of which are carcinogens.[5,6] Nicotine-derived nitrosamines in THS include 4-(methylnitrosamino)-1-(3pyridinyl)-1-butanone, and N-nitrosonornicotine,[5,6] which are found in secondhand smoke and have been associated with the development of lung cancer.[7] Ozone can react with nicotine to form formaldehyde, a known human carcinogen.[8]
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