Identifying Toxicologically Significant Compounds in Urban Wildfire Ash Using In Vitro Bioassays and High-Resolution Mass Spectrometry,Environmental Science & Technology

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Identifying Toxicologically Significant Compounds in Urban Wildfire Ash Using In Vitro Bioassays and High-Resolution Mass Spectrometry
Environmental Science & Technology ( IF 10.8 ) Pub Date : 2021-03-01 , DOI: 10.1021/acs.est.0c06712
Thomas M Young _{1,

2} , Gabrielle P Black _{1,

2} , Luann Wong ₁ , Clayton S Bloszies _{2,

3} , Oliver Fiehn _{2,

3} , Guochun He ₄ , Michael S Denison ₄ , Christoph F A Vogel _{4,

5} , Blythe Durbin-Johnson ₆

Affiliation

Urban wildfires may generate numerous unidentified chemicals of toxicity concern. Ash samples were collected from burned residences and from an undeveloped upwind reference site, following the Tubbs fire in Sonoma County, California. The solvent extracts of ash samples were analyzed using GC– and LC–high-resolution mass spectrometry (HRMS) and using a suite of in vitro bioassays for their bioactivity toward nuclear receptors [aryl hydrocarbon receptor (AhR), estrogen receptor (ER), and androgen receptor (AR)], their influence on the expression of genetic markers of stress and inflammation [interleukin-8 (IL-8) and cyclooxygenase-2 (COX-2)], and xenobiotic metabolism [cytochrome P4501A1 (CYP1A1)]. Genetic markers (CYP1A1, IL-8, and COX-2) and AhR activity were significantly higher with wildfire samples than in solvent controls, whereas AR and ER activities generally were unaffected or reduced. The bioassay responses of samples from residential areas were not significantly different from the samples from the reference site despite differing chemical compositions. Suspect and nontarget screening was conducted to identify the chemicals responsible for elevated bioactivity using the multiple streams of HRMS data and open-source data analysis workflows. For the bioassay endpoint with the largest available database of pure compound results (AhR), nontarget features statistically related to whole sample bioassay response using Spearman’s rank-order correlation coefficients or elastic net regression were significantly more likely (by 10 and 15 times, respectively) to be known AhR agonists than the overall population of compounds tentatively identified by nontarget analysis. The findings suggest that a combination of nontarget analysis, in vitro bioassays, and statistical analysis can identify bioactive compounds in complex mixtures.

中文翻译：

使用体外生物测定法和高分辨率质谱法鉴定城市野火灰中的毒理学重要化合物

城市野火可能会产生许多具有毒性的不明化学物质。在加利福尼亚州索诺玛县的塔布斯大火之后，从被烧毁的住宅和未开发的上风参考地点收集了灰烬样本。灰分样品的溶剂萃取物使用 GC 和 LC 高分辨率质谱 (HRMS) 并使用一套体外它们对核受体 [芳烃受体 (AhR)、雌激素受体 (ER) 和雄激素受体 (AR)] 的生物活性的生物测定，它们对压力和炎症的遗传标志物表达的影响 [白介素-8 (IL-8)和 cyclooxygenase-2 (COX-2)]，以及异生物质代谢 [细胞色素 P4501A1 (CYP1A1)]。野火样本的遗传标记（CYP1A1、IL-8 和 COX-2）和 AhR 活性显着高于溶剂对照，而 AR 和 ER 活性通常不受影响或降低。尽管化学成分不同，但来自住宅区的样品的生物测定响应与来自参考地点的样品没有显着差异。使用多个 HRMS 数据流和开源数据分析工作流程进行可疑和非目标筛选，以确定导致生物活性升高的化学物质。对于具有最大可用纯化合物结果数据库 (AhR) 的生物测定终点，使用 Spearman 秩相关系数或弹性净回归与全样本生物测定响应在统计学上相关的非目标特征的可能性显着增加（分别为 10 倍和 15 倍）是已知的 AhR 激动剂，而不是通过非目标分析初步鉴定的化合物的总体群体。研究结果表明，结合非目标分析，使用 Spearman 的秩相关系数或弹性净回归与全样本生物测定响应在统计学上相关的非目标特征明显更可能（分别为 10 倍和 15 倍）是已知的 AhR 激动剂，而不是通过非目标分析初步鉴定的化合物的总体群体。研究结果表明，结合非目标分析，使用 Spearman 的秩相关系数或弹性净回归与全样本生物测定响应在统计学上相关的非目标特征明显更可能（分别为 10 倍和 15 倍）是已知的 AhR 激动剂，而不是通过非目标分析初步鉴定的化合物的总体群体。研究结果表明，结合非目标分析，体外生物测定和统计分析可以识别复杂混合物中的生物活性化合物。

更新日期：2021-03-16

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