Radiation-Induced Bystander Effect on the Genome of Bone Marrow Mesenchymal Stem Cells in Lung Cancer

• Published in: Antioxidants & redox signaling Vol. 38; no. 10-12; p. 747
• Main Authors: Zhang, Yi-Ming, Zhang, Li-Ying, Li, Yang-Yang, Zhou, Heng, Miao, Zhi-Ming, Liu, Zhi-Wei, Zhou, Gu-Cheng, Zhou, Ting, Niu, Fan, Li, Jing, Hong, Tao, He, Jin-Peng, Ding, Nan, Zhang, Ya-Nan, Hua, Jun-Rui, Wang, Ju-Fang, Liu, Yong-Qi
• Format: Journal Article
• Language: English
• Published: United States 01.04.2023
• Subjects: Bystander Effect - radiation effects; Genomic Instability; Humans; Lung Neoplasms - metabolism; Mesenchymal Stem Cells - metabolism; Transforming Growth Factor beta1 - metabolism; Tumor Necrosis Factor-alpha - metabolism; Tumor Necrosis Factor-alpha - pharmacology; lung cancer; TNF-α; genome instability; TGF-β1; HIF-1α; RIBE; BMSCs
• ISSN: 1557-7716
• DOI: 10.1089/ars.2022.0072

Radiation by-radiation effect (RIBE) can induce the genomic instability of bone marrow mesenchymal stem cells (BMSCs) adjacent to lung cancer, and this effect not only exists in the short-term, but also accompanies it in the long-term, but its specific mechanism is not clear. Our goal is to explore the similarities and differences in the mechanism of genomic damage in tumor-associated BMSCs induced by short-term and long-term RIBE, and to provide a theoretical basis for adjuvant drugs for protection against RIBE at different clinical time periods. We found that both short- and long-term RIBE induced genomic instability. We could show a high expression of TGF-β1, TNF-α, and HIF-1α in tumor-associated BMSCs after short-term RIBE whereas only TNF-α and HIF-1α expression was increased in long-term RIBE. We further confirmed that genomic instability is associated with the activation of the HIF-1α pathway and that this is mediated by TNF-α and TGF-β1. In addition, we found differences in the mechanisms of genomic instability in the considered RIBE windows of analysis. In short-term RIBE, both TNF-α and TGF-β1 play a role, whereas only TNF-α plays a decisive role in long-term RIBE. In addition, there were differences in BMSC recruitment and genomic instability of different tissues with a more pronounced expression in tumor and bone marrow than compared to lung. We could show dynamic changes in the expression of the cytokines TGF-β1 and TNF-α during short- and long-term RIBE. The differential expression of the two is the key to causing the genomic damage of tumor-associated BMSCs in the considered windows of analysis. Therefore, these results may serve as a guideline for the administration of radiation protection adjuvant drugs at different clinical stages. 38, 747-767.