暴露于空气中的月球尘埃的大鼠肺中与炎症和纤维化有关的基因表达的持续变化。

IF 2 4区 医学 Q4 TOXICOLOGY
Ye Zhang, Michael Story, Samrawit Yeshitla, Xiaoyu Wang, Robert R Scully, Corey Theriot, Honglu Wu, Valerie E Ryder, Chiu-Wing Lam
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引用次数: 1

摘要

美国宇航局目前正计划重返月球进行进一步的探索和研究。月球被一层潜在的活性细尘覆盖,这可能对探险者造成毒性风险。为了评估这种风险,我们将大鼠暴露在阿波罗14号任务期间收集的月球尘埃(LD)中。将大鼠暴露于浓度为0、2.1、6.8、20.8或60.6 mg/m3的可呼吸大小的LD中4周。在暴露13周后,我们评估了44,000个基因转录本,发现614个已知功能基因的表达在暴露于2个较高浓度的LD的大鼠中显著改变,而暴露于最低浓度LD的组中几乎没有检测到基因表达的变化。许多基因表达的显著变化涉及已知与炎症或纤维化相关的基因。使用实时聚合酶链反应进一步分析了4周粉尘暴露后第1天、第1周、第4周和第13周所有采样点的4个编码促炎趋化因子的基因。这些基因的表达以剂量和时间依赖的方式改变,并且在暴露于两种较高浓度的LD的大鼠的肺部持续变化。它们的表达与我们在先前的研究中在这些动物的肺毒性生物标志物和病理学中检测到的变化一致。由于阿波罗-14 LD含有类似于亚利桑那州火山灰的常见矿物氧化物,除了揭示LD的毒性外,我们的发现还有助于阐明陆地矿物粉尘诱导肺毒性的基因组和分子机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Persistent changes in expression of genes involved in inflammation and fibrosis in the lungs of rats exposed to airborne lunar dust.

NASA is currently planning return missions to the Moon for further exploration and research. The Moon is covered by a layer of potentially reactive fine dust, which could pose a toxicological risk of exposure to explorers. To assess this risk, we exposed rats to lunar dust (LD) that was collected during the Apollo14 mission. Rats were exposed to respirable sizes of LD at concentrations of 0, 2.1, 6.8, 20.8, or 60.6 mg/m3 for 4 weeks. At thirteen  weeks after exposure, we assessed 44,000 gene transcripts and found the expression of 614 genes with known functions were significantly altered in the rats exposed to the 2 higher concentrations of LD, whereas few changes in gene expression were detected in the group exposed to the lowest concentration of LD. Many of the significant changes in gene expression involved genes known to be associated with inflammation or fibrosis. Four genes encoding pro-inflammatory chemokines were analyzed further for all the sampling points at 1 day, and 1, 4, and 13 weeks after the 4-week dust exposure, using real-time polymerase chain reaction. The expression of these genes was altered in a dose- and time-dependent manner and persistently changed in the lungs of the rats exposed to the two higher concentrations of LD. Their expressions are consistent with changes we detected in pulmonary toxicity biomarkers and pathology in these animals during a previous study. Because Apollo-14 LD contains common mineral oxides similar to an Arizona volcanic ash, besides revealing the toxicity of LD, our findings could help elucidate the genomic and molecular mechanisms involved in pulmonary toxicity induced by terrestrial mineral dusts.

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来源期刊
Inhalation Toxicology
Inhalation Toxicology 医学-毒理学
CiteScore
4.10
自引率
4.80%
发文量
38
审稿时长
6-12 weeks
期刊介绍: Inhalation Toxicology is a peer-reviewed publication providing a key forum for the latest accomplishments and advancements in concepts, approaches, and procedures presently being used to evaluate the health risk associated with airborne chemicals. The journal publishes original research, reviews, symposia, and workshop topics involving the respiratory system’s functions in health and disease, the pathogenesis and mechanism of injury, the extrapolation of animal data to humans, the effects of inhaled substances on extra-pulmonary systems, as well as reliable and innovative models for predicting human disease.
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