众所周知，吸烟与基因变化均为诱发各种癌症的重要因素。不过，相当多的癌症患者，既无吸烟史，又无遗传史。此外，短期接触三手烟对于基因的影响亦不明确。
三手烟是指吸烟后残留于衣服、墙壁、家具、地毯、靠垫，甚至头发和皮肤等的烟草残余化学物，亦称非自愿吸烟，属于一种被动吸烟方式，也是目前危害最广泛、最严重的室内空气污染。吸烟者即使吸烟时开窗、开风扇或空调，都无法消除三手烟。吸烟者即使在户外吸烟，烟草残余化学物仍附着于吸烟者身上，当吸烟者回到室内，这些有毒物质便四处传播。那些凝结在物件表面的有毒物质，可残留数周、数月甚至数年。
根据世界卫生组织报告，三手烟约有4000多种化学品，其中至少有250种已知有害物质、50多种已知可致癌物质。虽然目前还不能分类研究这些物质在布料以及墙壁上的准确附着时间，但是至少在短时间内，这些附着的有害物质不会轻易消散。三手烟有毒物质包括用于化学武器的氢氰酸、用于打火机油的丁烷、用于油漆稀释剂的甲苯，此外还有砷、铅、一氧化碳、甲醛、亚硝胺、甚至高度放射性物质钋210等。
2019年6月28日，《美国医学会杂志》网络开放版在线发表加利福尼亚大学河滨分校、加利福尼亚大学旧金山分校的研究报告，分析了健康不吸烟女性短期接触三手烟对鼻上皮细胞基因表达的影响。
该随机交叉临床研究于2011～2015年入组日常生活从未吸入二手烟的26位健康不吸烟者，在实验室环境下，仅头部先后暴露于过滤干净空气、三手烟环境，各持续3小时，间隔至少21天，先后顺序随机。暴露前后，收集其中8位女性和5位男性的鼻上皮标本，并对基因转录分子核糖核酸（RNA）进行测序，分析基因表达变化。
结果，仅从4位健康不吸烟女性获得足够标本进行RNA测序，凑巧这些女性均先暴露于过滤干净空气、间隔至少21天后暴露于三手烟环境，年龄27～49岁，平均42±10.2岁，均无慢性疾病史。这些女性暴露于过滤干净空气3小时后仅2个基因表达发生变化，而暴露于三手烟3小时后共计389个基因表达发生变化，包括：
应激诱发的线粒体过度融合相关变化：例如呼吸电子传递链（Q=2.84×10-3）、线粒体内膜（Q=7.21×10-6）
脱氧核糖核酸修复机制上调相关变化：例如核苷酸切除修复（Q=1.05×10-2）
该研究还通过独创通路富集分析确定了相关典型通路变化，例如：
应激诱发的线粒体过度融合相关变化（例如氧化磷酸化增加，P=0.001）
氧化应激变化（例如谷胱甘肽耗竭II期反应，P=0.04）
细胞生存和细胞死亡抑制相关变化（Z=5.026）
人类鼻上皮细胞暴露于二手烟的基因表达变化富集分析
人类鼻上皮对三手烟的反应总结示意图
因此，该研究结果表明，短期接触三手烟可以引起细胞应激，从而激活细胞生存和细胞死亡抑制相关通路基因表达变化，某些反应类似既往体外研究证实的应激诱发线粒体过度融合，这些数据可能有助医生治疗暴露于三手烟的患者，也可能有助于制定防止三手烟污染环境的法规。
有趣的是，全世界首例转基因植物（含有抗生素类抗体的烟草）于1983年在美国成功培植，世界烟草七项指标（种植面积、收购量、生产量、消费量、吸烟人数、烟草利税、死于吸烟相关疾病人数）排名第一的中国于1992年首先在大田种植抗黄瓜花叶病毒转基因烟草，成为全世界首个商品化种植转基因作物的国家。美国食品药品管理局直至1994年才允许转基因食品（番茄）上市销售，可是25年来大众谈之色变的转基因食品并未明确改变人类基因，而三手烟改变大量人类基因仅需3小时。
JAMA Netw Open. 2019 Jun 28;2(6):e196362.
Experimental Acute Exposure to Thirdhand Smoke and Changes in the Human Nasal Epithelial Transcriptome: A Randomized Clinical Trial.
Giovanna L. Pozuelos; Meenakshi S. Kagda; Suzaynn Schick; Thomas Girke; David C. Volz; Prue Talbot.
University of California, Riverside; University of California, San Francisco.
This randomized clinical trial compares changes in the transcriptome of the human nasal epithelium in healthy, nonsmoking women who were first exposed to clean air and later exposed to thirdhand smoke.
QUESTION: Does acute inhalation of thirdhand smoke alter the transcriptome of the human nasal epithelium?
FINDINGS: This randomized clinical trial exposed 4 healthy, nonsmoking women to clean air, which altered the expression of only 2 genes. When the same women were exposed to thirdhand smoke at least 21 days later, 389 genes associated with cell stress and survival pathways were differentially expressed, and many affected genes were associated with increased mitochondrial activity, oxidative stress, DNA repair, cell survival, and inhibition of cell death.
MEANING: These results suggest that acute exposure to thirdhand smoke stresses the human nasal epithelium, a finding that may be valuable to physicians treating exposed patients.
IMPORTANCE: No previous studies have shown that acute inhalation of thirdhand smoke (THS) activates stress and survival pathways in the human nasal epithelium.
OBJECTIVE: To evaluate gene expression in the nasal epithelium of nonsmoking women following acute inhalation of clean air and THS.
DESIGN, SETTING, AND PARTICIPANTS: 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.
EXPOSURES: By chance, women in the subset were randomized to receive clean air exposure first and THS exposure second. Exposures lasted 3 hours.
MAIN OUTCOMES AND MEASURES: Differentially expressed genes were identified using RNA sequencing with a false-discovery rate less than 0.1.
RESULTS: 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).
CONCLUSIONS AND RELEVANCE: 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.
DOI: 10.1001/jamanetworkopen.2019.6362
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