Aerosol physicochemical determinants of carbon black and ozone inhalation co-exposure induced pulmonary toxicity.
Aerosol physicochemical determinants of carbon black and ozone inhalation co-exposure induced pulmonary toxicity.
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DOI：
10.1093/toxsci/kfac113
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发表时间：
2023-01-31
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影响因子：
--
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中科院分区：
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空气污染导致全球700多万人过早死亡。使用超细炭黑（CB）和臭氧（O3）作为环境共暴露情景的模型，通过产生、表征和比较稳定浓度的CB气溶胶，确定急性肺损伤和炎症的剂量反应关系（2.5、5.0、10.0 mg/m3）、O3（0.5、1.0、2.0 ppm）与CB+O3（2.5 + 0.5、5.0 + 1.0、10.0 + 2.0）混合物。C57 BL 6雄性小鼠通过全身吸入暴露3小时，24小时后测定急性毒性。CB本身没有引起任何改变，但是，O3和CB+O3观察到肺损伤/炎症的剂量反应。这种增加与混合物的响应是不依赖于摄取，但由于增强的颗粒的反应性。基准剂量建模显示，与单独的CB或O3相比，CB+O3的效力增加了数倍。主成分分析提供了不同剂量和治疗之间的反应关系的见解。有一个显着的相关性，肺反应与基于电荷的大小分布，总/肺泡沉积，氧化剂的产生和抗氧化剂消耗潜力。肺组织基因/蛋白质反应表现出不同的模式，可以通过颗粒剂量/气溶胶反应（IL-1β、KC、TGF-β）和颗粒反应性（TSLP、IL-13、IL-6）更好地预测。分层聚类显示高剂量的独特特征和低和中剂量CB+O3的mRNA表达模式的相似性。总之，我们证明了CB+O3共同暴露的生物学结果显着大于在一个范围内的气溶胶浓度和气溶胶特性可以预测生物学结果的个人暴露。
Air pollution accounts for more than 7 million premature deaths worldwide. Using ultrafine carbon black (CB) and ozone (O3) as a model for an environmental co-exposure scenario, the dose response relationships in acute pulmonary injury and inflammation were determined by generating, characterizing, and comparing stable concentrations of CB aerosols (2.5, 5.0, 10.0 mg/m3), O3 (0.5, 1.0, 2.0 ppm) with mixture CB+O3 (2.5 + 0.5, 5.0 + 1.0, 10.0 + 2.0). C57BL6 male mice were exposed for 3 hours by whole body inhalation and acute toxicity determined after 24h. CB itself did not cause any alteration, however, a dose response in pulmonary injury/inflammation was observed with O3 and CB+O3. This increase in response with mixtures was not dependent on the uptake but due to enhanced reactivity of the particles. Benchmark dose modeling showed several-fold increase in potency with CB+O3 compared to CB or O3 alone. Principal component analysis provided insight into response relationships between various doses and treatments. There was a significant correlation in lung responses with charge-based size distribution, total/alveolar deposition, oxidant generation and antioxidant depletion potential. Lung tissue gene/protein response demonstrated distinct patterns that are better predicted by either particle dose/aerosol responses (IL-1β, KC, TGF-β) particle reactivity (TSLP, IL13, IL-6). Hierarchical clustering showed a distinct signature with high dose and a similarity in mRNA expression pattern of low and medium doses of CB+O3. In conclusion, we demonstrate that the biological outcomes from CB+O3 co-exposure are significantly greater than individual exposures over a range of aerosol concentrations and aerosol characteristics can predict biological outcome.
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影响因子：
6.8
作者：
Caceres, Lourdes;Paz, Mariela L.;Evelson, Pablo
通讯作者：
Evelson, Pablo
影响因子：
3.8
作者：
Hatch GE;McKee J;Brown J;McDonnell W;Seal E;Soukup J;Slade R;Crissman K;Devlin R
通讯作者：
Devlin R
影响因子：
10
作者：
Fraser K;Kodali V;Yanamala N;Birch ME;Cena L;Casuccio G;Bunker K;Lersch TL;Evans DE;Stefaniak A;Hammer MA;Kashon ML;Boots T;Eye T;Hubczak J;Friend SA;Dahm M;Schubauer-Berigan MK;Siegrist K;Lowry D;Bauer AK;Sargent LM;Erdely A
通讯作者：
Erdely A
影响因子：
10
作者：
Braakhuis HM;Park MV;Gosens I;De Jong WH;Cassee FR
通讯作者：
Cassee FR
DOI：
10.3233/jad-170658
发表时间：
2018
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Cleary EG;Cifuentes M;Grinstein G;Brugge D;Shea TB
通讯作者：
Shea TB