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一种改良的气体暴露系统在烟草烟雾毒物体外毒理学评估中的应用。

Application of a modified gaseous exposure system to the in vitro toxicological assessment of tobacco smoke toxicants.

作者信息

Breheny Damien, Cunningham Fiona, Kilford Joanne, Payne Rebecca, Dillon Deborah, Meredith Clive

机构信息

British American Tobacco, Group R&D, Southampton, Hampshire, SO15 8TL, United Kingdom.

出版信息

Environ Mol Mutagen. 2014 Oct;55(8):662-72. doi: 10.1002/em.21876. Epub 2014 Jun 2.

Abstract

Tobacco smoke is a complex mixture of over 6,000 individual chemical constituents. Approximately 150 of these have been identified as 'tobacco smoke toxicants' due to their known toxicological effects. A number of these toxicants are present in the gaseous phase of tobacco smoke. This presents a technical challenge when assessing the toxicological effects of these chemicals in vitro. We have adapted a commercially available tobacco smoke exposure system to enable the assessment of the contribution of individual smoke toxicants to the overall toxicological effects of whole mainstream cigarette smoke (WS). Here we present a description of the exposure system and the methodology used. We use the example of a gaseous tobacco smoke toxicant, ethylene oxide (EtO), a Group 1 IARC carcinogen and known mutagen, to illustrate how this methodology can be applied to the assessment of genotoxicity of gaseous chemicals in the context of WS. In the present study we found that EtO was positive in Salmonella typhimurium strain YG1042, a strain that is sensitive to tobacco smoke. However, EtO did not increase the mutagenicity of the WS mixture when it was added at greatly higher concentrations than those found typically in WS. The findings presented here demonstrate the suitability of this exposure system for the assessment of the mutagenic potential of gases in vitro. Whilst we have focused on tobacco smoke toxicants, this system has broad application potential in studying the biological effects of exposure to a wide range of gaseous compounds that are present within complex aerosol mixtures.

摘要

烟草烟雾是由6000多种单独化学成分组成的复杂混合物。其中约150种已被确定为“烟草烟雾毒物”,因其已知的毒理学效应。这些毒物中有许多存在于烟草烟雾的气相中。在体外评估这些化学物质的毒理学效应时,这带来了技术挑战。我们对一种市售的烟草烟雾暴露系统进行了改进,以评估单个烟雾毒物对整个主流香烟烟雾(WS)总体毒理学效应的贡献。在此,我们介绍该暴露系统及所使用的方法。我们以气态烟草烟雾毒物环氧乙烷(EtO)为例,它是国际癌症研究机构第1组致癌物且是已知的诱变剂,来说明该方法如何应用于在WS背景下评估气态化学物质的遗传毒性。在本研究中,我们发现EtO在对烟草烟雾敏感的鼠伤寒沙门氏菌菌株YG1042中呈阳性。然而,当以比WS中通常发现的浓度高得多的浓度添加EtO时,它并未增加WS混合物的诱变性。此处呈现的研究结果证明了该暴露系统适用于体外评估气体的诱变潜力。虽然我们专注于烟草烟雾毒物,但该系统在研究暴露于复杂气溶胶混合物中存在的多种气态化合物的生物学效应方面具有广泛的应用潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31b9/6710645/59b689b2c17e/EM-55-662-g001.jpg

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