Yiying Gao,Xugang Li,Jingjing Gao,Zhen Zhang,Yang Feng,Jihua Nie,Wei Zhu,Shuyu Zhang,Jianping Cao
Radiation-induced lung injury is a major dose-limiting toxicity that occurs due to thoracic radiotherapy. Metabolomics is a powerful quantitative measurement of low-molecular-weight metabolites in response to environmental disturbances. However, the metabolomic profiles of radiation-induced lung injury have not been reported yet. In this study, male Sprague-Dawley rats were subjected to a single dose of 10 or 20 Gy irradiation to the right lung. One week after radiation, the obvious morphological alteration of lung tissues after radiation was observed by hematoxylin and eosin staining through a transmission electron microscope. We then analyzed the metabolites and related pathways of radiation-induced lung injury by gas chromatography–mass spectrometry, and a total of 453 metabolites were identified. Compared to the nonirradiated left lung, 19 metabolites (8 upregulated and 11 downregulated) showed a significant difference in 10 Gy irradiated lung tissues, including mucic acid, methyl-β-d-galactopyranoside, quinoline-4-carboxylic acid, and pyridoxine. There were 31 differential metabolites (16 upregulated and 15 downregulated) between 20 Gy irradiated and nonirradiated lung tissues, including taurine, piperine, 1,2,4-benzenetriol, and lactamide. The Kyoto Encyclopedia of Genes and Genomes–based pathway analysis enriched 32 metabolic pathways between the irradiated and nonirradiated lung tissues, including pyrimidine metabolism, ATP-binding cassette transporters, aminoacyl-tRNA biosynthesis, and β-alanine metabolism. Among the dysregulated metabolites, we found that taurine promoted clonogenic survival and reduced radiation-induced necrosis in human embryonic lung fibroblast (HELF) cells. This study provides evidence indicating that radiation induces metabolic alterations of the lung. These findings significantly advance our understanding of the pathophysiology of radiation-induced lung injury from the perspective of metabolism.
Background Gadolinium-based nanoparticles (GdNPs) have been used as theranostic sensitizers in clinical radiotherapy studies; however, the biomechanisms underlying the radio-sensitizing effects of GdNPs have yet to be determined. In this study, ultra-small gadolinium oxide nanocrystals (GONs) were employed to investigate their radiosensitizing effects and biological mechanisms in non-small-cell lung cancer (NSCLC) cells under X-ray irradiation. Method and materials GONs were synthesized using polyol method. Hydroxyl radical production, oxidative stress, and clonogenic survival after X-ray irradiation were used to evaluate the radiosensitizing effects of GONs. DNA double-strand breakage, cell cycle phase, and apoptosis and autophagy incidences were investigated in vitro to determine the radiosensitizing biomechanism of GONs under X-ray irradiation. Results GONs induced hydroxyl radical production and oxidative stress in a dose- and concentration-dependent manner in NSCLC cells after X-ray irradiation. The sensitizer enhancement ratios of GONs ranged between 19.3% and 26.3% for the NSCLC cells under investigation with a 10% survival rate compared with that of the cells treated with irradiation alone. Addition of 3-methyladenine to the cell medium decreased the incidence rate of autophagy and increased cell survival, supporting the idea that the GONs promoted cytostatic autophagy in NSCLC cells under X-ray irradiation. Conclusion This study examined the biological mechanisms underlying the radiosensitizing effects of GONs on NSCLC cells and presented the first evidence for the radiosensitizing effects of GONs via activation of cytostatic autophagy pathway following X-ray irradiation.
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