Metabolomics analysis of pathways underlying radiation-induced salivary gland dysfunction stages

• Published in: PloS one Vol. 18; no. 11; p. e0294355
• Main Authors: Buss, Lauren G, De Oliveira Pessoa, Diogo, Snider, Justin M, Padi, Megha, Martinez, Jessica A, Limesand, Kirsten H
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.11.2023; Public Library of Science (PLoS)
• Subjects: Amino acids; Analysis; Animals; Annotations; Cancer; Cancer therapies; Carbon; Carbon - metabolism; Care and treatment; Chromatography; Complications and side effects; Diagnosis; Enrichment; Evaluation; Exocrine glands; Glutathione; Glutathione - metabolism; Head & neck cancer; Head and neck cancer; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - radiotherapy; High performance liquid chromatography; Humans; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Medical research; Medicine, Experimental; Metabolism; Metabolites; Metabolomics; Mice; Network analysis; Nuclear energy; Parotid Gland - radiation effects; Patient outcomes; Physiological aspects; Radiation; Radiation damage; Radiation effects; Radiation therapy; Radiotherapy; Salivary gland; Salivary glands; Salivary Glands - metabolism; Scientific imaging; Solvents; Tumors; Xerostomia - metabolism; United States
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0294355

Salivary gland hypofunction is an adverse side effect associated with radiotherapy for head and neck cancer patients. This study delineated metabolic changes at acute, intermediate, and chronic radiation damage response stages in mouse salivary glands following a single 5 Gy dose. Ultra-high performance liquid chromatography-mass spectrometry was performed on parotid salivary gland tissue collected at 3, 14, and 30 days following radiation (IR). Pathway enrichment analysis, network analysis based on metabolite structural similarity, and network analysis based on metabolite abundance correlations were used to incorporate both metabolite levels and structural annotation. The greatest number of enriched pathways are observed at 3 days and the lowest at 30 days following radiation. Amino acid metabolism pathways, glutathione metabolism, and central carbon metabolism in cancer are enriched at all radiation time points across different analytical methods. This study suggests that glutathione and central carbon metabolism in cancer may be important pathways in the unresolved effect of radiation treatment.