眾所周知，吸煙與基因變化均為誘發(fā)各種癌癥的重要因素。不過，相當(dāng)多的癌癥患者，既無吸煙史，又無遺傳史。此外，短期接觸三手煙對于基因的影響亦不明確。
三手煙是指吸煙后殘留于衣服、墻壁、家具、地毯、靠墊，甚至頭發(fā)和皮膚等的煙草殘余化學(xué)物，亦稱非自愿吸煙，屬于一種被動吸煙方式，也是目前危害最廣泛、最嚴重的室內(nèi)空氣污染。吸煙者即使吸煙時開窗、開風(fēng)扇或空調(diào)，都無法消除三手煙。吸煙者即使在戶外吸煙，煙草殘余化學(xué)物仍附著于吸煙者身上，當(dāng)吸煙者回到室內(nèi)，這些有毒物質(zhì)便四處傳播。那些凝結(jié)在物件表面的有毒物質(zhì)，可殘留數(shù)周、數(shù)月甚至數(shù)年。
根據(jù)世界衛(wèi)生組織報告，三手煙約有4000多種化學(xué)品，其中至少有250種已知有害物質(zhì)、50多種已知可致癌物質(zhì)。雖然目前還不能分類研究這些物質(zhì)在布料以及墻壁上的準確附著時間，但是至少在短時間內(nèi)，這些附著的有害物質(zhì)不會輕易消散。三手煙有毒物質(zhì)包括用于化學(xué)武器的氫氰酸、用于打火機油的丁烷、用于油漆稀釋劑的甲苯，此外還有砷、鉛、一氧化碳、甲醛、亞硝胺、甚至高度放射性物質(zhì)釙210等。
2019年6月28日，《美國醫(yī)學(xué)會雜志》網(wǎng)絡(luò)開放版在線發(fā)表加利福尼亞大學(xué)河濱分校、加利福尼亞大學(xué)舊金山分校的研究報告，分析了健康不吸煙女性短期接觸三手煙對鼻上皮細胞基因表達的影響。
該隨機交叉臨床研究于2011～2015年入組日常生活從未吸入二手煙的26位健康不吸煙者，在實驗室環(huán)境下，僅頭部先后暴露于過濾干凈空氣、三手煙環(huán)境，各持續(xù)3小時，間隔至少21天，先后順序隨機。暴露前后，收集其中8位女性和5位男性的鼻上皮標本，并對基因轉(zhuǎn)錄分子核糖核酸（RNA）進行測序，分析基因表達變化。
結(jié)果，僅從4位健康不吸煙女性獲得足夠標本進行RNA測序，湊巧這些女性均先暴露于過濾干凈空氣、間隔至少21天后暴露于三手煙環(huán)境，年齡27～49歲，平均42±10.2歲，均無慢性疾病史。這些女性暴露于過濾干凈空氣3小時后僅2個基因表達發(fā)生變化，而暴露于三手煙3小時后共計389個基因表達發(fā)生變化，包括：
應(yīng)激誘發(fā)的線粒體過度融合相關(guān)變化：例如呼吸電子傳遞鏈（Q=2.84×10-3）、線粒體內(nèi)膜（Q=7.21×10-6）
脫氧核糖核酸修復(fù)機制上調(diào)相關(guān)變化：例如核苷酸切除修復(fù)（Q=1.05×10-2）
該研究還通過獨創(chuàng)通路富集分析確定了相關(guān)典型通路變化，例如：
應(yīng)激誘發(fā)的線粒體過度融合相關(guān)變化（例如氧化磷酸化增加，P=0.001）
氧化應(yīng)激變化（例如谷胱甘肽耗竭II期反應(yīng)，P=0.04）
細胞生存和細胞死亡抑制相關(guān)變化（Z=5.026）
人類鼻上皮細胞暴露于二手煙的基因表達變化富集分析
人類鼻上皮對三手煙的反應(yīng)總結(jié)示意圖
因此，該研究結(jié)果表明，短期接觸三手煙可以引起細胞應(yīng)激，從而激活細胞生存和細胞死亡抑制相關(guān)通路基因表達變化，某些反應(yīng)類似既往體外研究證實的應(yīng)激誘發(fā)線粒體過度融合，這些數(shù)據(jù)可能有助醫(yī)生治療暴露于三手煙的患者，也可能有助于制定防止三手煙污染環(huán)境的法規(guī)。
有趣的是，全世界首例轉(zhuǎn)基因植物（含有抗生素類抗體的煙草）于1983年在美國成功培植，世界煙草七項指標（種植面積、收購量、生產(chǎn)量、消費量、吸煙人數(shù)、煙草利稅、死于吸煙相關(guān)疾病人數(shù)）排名第一的中國于1992年首先在大田種植抗黃瓜花葉病毒轉(zhuǎn)基因煙草，成為全世界首個商品化種植轉(zhuǎn)基因作物的國家。美國食品藥品管理局直至1994年才允許轉(zhuǎn)基因食品（番茄）上市銷售，可是25年來大眾談之色變的轉(zhuǎn)基因食品并未明確改變?nèi)祟惢?，?/span>三手煙改變大量人類基因僅需3小時。
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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