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未燃烧烟草香烟烟雾改变大鼠肺气道超微结构和DNA。

Unburned Tobacco Cigarette Smoke Alters Rat Ultrastructural Lung Airways and DNA.

作者信息

Vivarelli Fabio, Canistro Donatella, Cirillo Silvia, Elias Ryan J, Granata Silvia, Mussoni Matilde, Burattini Sabrina, Falcieri Elisabetta, Turrini Eleonora, Fimognari Carmela, Buschini Annamaria, Lazzaretti Mirca, Beghi Sofia, Girotti Stefano, Sangiorgi Stefano, Bolelli Luca, Ghini Severino, Ferri Elida Nora, Fagiolino Ivan, Franchi Paola, Lucarini Marco, Mercatante Dario, Rodriguez-Estrada Maria Teresa, Lorenzini Antonello, Marchionni Silvia, Gabriele Morena, Longo Vincenzo, Paolini Moreno

机构信息

Department of Pharmacy and Biotechnology, Alma Mater Studiorum-University of Bologna, Bologna,Italy.

Department of Food Science, College of Agricultural Sciences, Pennsylvania State University, University Park, PA, USA.

出版信息

Nicotine Tob Res. 2021 Nov 5;23(12):2127-2134. doi: 10.1093/ntr/ntab108.

DOI:10.1093/ntr/ntab108
PMID:34036368
Abstract

INTRODUCTION

Recently, the Food and Drug Administration authorized the marketing of IQOS Tobacco Heating System as a Modified Risk Tobacco Product based on an electronic heat-not-burn technology that purports to reduce the risk.

METHODS

Sprague-Dawley rats were exposed in a whole-body mode to IQOS aerosol for 4 weeks. We performed the chemical characterization of IQOS mainstream and we studied the ultrastructural changes in trachea and lung parenchyma of rats exposed to IQOS stick mainstream and tissue pro-inflammatory markers. We investigated the reactive oxygen species amount along with the markers of tissue and DNA oxidative damage. Moreover, we tested the putative genotoxicity of IQOS mainstream through Ames and alkaline Comet mutagenicity assays.

RESULTS

Here, we identified irritating and carcinogenic compounds including aldehydes and polycyclic aromatic hydrocarbons in the IQOS mainstream as sign of incomplete combustion and degradation of tobacco, that lead to severe remodelling of smaller and largest rat airways. We demonstrated that IQOS mainstream induces lung enzymes that activate carcinogens, increases tissue reactive radical concentration; promotes oxidative DNA breaks and gene level DNA damage; and stimulates mitogen activated protein kinase pathway which is involved in the conventional tobacco smoke-induced cancer progression.

CONCLUSIONS

Collectively, our findings reveal that IQOS causes grave lung damage and promotes factors that increase cancer risk.

IMPLICATIONS

IQOS has been proposed as a safer alternative to conventional cigarettes, due to depressed concentration of various harmful constituents typical of traditional tobacco smoke. However, its lower health risks to consumers have yet to be determined. Our findings confirm that IQOS mainstream contains pyrolysis and thermogenic degradation by-products, the same harmful constituents of traditional cigarette smoke, and, for the first time, we show that it causes grave lung damage and promotes factors that increase cancer risk in the animal model.

摘要

引言

最近,美国食品药品监督管理局批准了IQOS烟草加热系统作为一种风险降低型烟草产品进行销售,该系统基于一种声称能降低风险的电子加热不燃烧技术。

方法

将斯普拉格-道利大鼠以全身暴露模式暴露于IQOS气溶胶中4周。我们对IQOS主流气溶胶进行了化学表征,并研究了暴露于IQOS烟弹主流气溶胶的大鼠气管和肺实质的超微结构变化以及组织促炎标志物。我们调查了活性氧的含量以及组织和DNA氧化损伤的标志物。此外,我们通过艾姆斯试验和碱性彗星试验测试了IQOS主流气溶胶的潜在遗传毒性。

结果

在此,我们在IQOS主流气溶胶中鉴定出刺激性和致癌性化合物,包括醛类和多环芳烃,这是烟草不完全燃烧和降解的迹象,会导致大鼠大小气道的严重重塑。我们证明,IQOS主流气溶胶会诱导激活致癌物的肺酶,增加组织活性自由基浓度;促进氧化性DNA断裂和基因水平的DNA损伤;并刺激丝裂原活化蛋白激酶途径,该途径参与传统烟草烟雾诱导的癌症进展。

结论

总体而言,我们的研究结果表明,IQOS会造成严重的肺部损伤并促进增加癌症风险的因素。

启示

由于传统烟草烟雾中各种有害成分的浓度降低,IQOS被提议作为传统香烟的一种更安全的替代品。然而,其对消费者较低的健康风险尚未确定。我们的研究结果证实,IQOS主流气溶胶含有热解和热降解副产物,与传统香烟烟雾中的有害成分相同,并且,我们首次表明,它会在动物模型中造成严重的肺部损伤并促进增加癌症风险的因素。

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