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  3. Radiation-induced bystander effect on the genome of bone marrow mesenchymal stem cells in lung cancer

Radiation-induced bystander effect on the genome of bone marrow mesenchymal stem cells in lung cancer

  • Antioxid Redox Signal. 2022 Oct 14. doi: 10.1089/ars.2022.0072.
Yiming Zhang 1,  Liying Zhang 2,  Yangyang Li 3,  Heng Zhou 4,  Zhiming Miao 5,  Zhiwei Liu 6,  Gucheng Zhou 7,  Ting Zhou 8,  Fan Niu 9,  Jing Li 10,  Tao Hong 11,  Jinpeng He 12,  Nan Ding 13,  Yanan Zhang 14,  Junrui Hua 15,  Jufang Wang 16,  Yongqi Liu 17
Affiliations

Affiliations

  • 1 Gansu University of Traditional Chinese Medicine, 381940, Lanzhou, Gansu, China; 327620132@qq.com.
  • 2 Gansu University of Traditional Chinese Medicine, 381940, Lanzhou, Gansu, China; zhangliying201212@163.com.
  • 3 Gansu University of Traditional Chinese Medicine, 381940, No. 35, Dingxi East Road, Chengguan District, Lanzhou City, Gansu Province, Lanzhou, China, 730000; 1576376429@qq.com.
  • 4 Institute of Modern Physics Chinese Academy of Sciences, 71200, Lanzhou, Gansu, China; hengzhou@impcas.ac.cn.
  • 5 Gansu University of Traditional Chinese Medicine, 381940, Lanzhou, Gansu, China; 2280140806@qq.com.
  • 6 Gansu University of Traditional Chinese Medicine, 381940, Lanzhou, Gansu, China; 2269958141@qq.com.
  • 7 Gansu University of Traditional Chinese Medicine, 381940, Lanzhou, Gansu, China; 526361725@qq.com.
  • 8 Gansu University of Traditional Chinese Medicine, 381940, Lanzhou, Gansu, China; zhouting0225@163.com.
  • 9 Gansu University of Traditional Chinese Medicine, 381940, Lanzhou, Gansu, China; 2210214636@qq.com.
  • 10 Gansu University of Traditional Chinese Medicine, 381940, Lanzhou, Gansu, China; 2257518207@qq.com.
  • 11 Gansu University of Traditional Chinese Medicine, 381940, Lanzhou, Gansu, China; 735488702@qq.com.
  • 12 Institute of Modern Physics Chinese Academy of Sciences, 71200, Lanzhou, Gansu, China; hejp03@163.com.
  • 13 Institute of Modern Physics Chinese Academy of Sciences, 71200, Lanzhou, Gansu, China; dn@impcas.ac.cn.
  • 14 Institute of Modern Physics Chinese Academy of Sciences, 71200, Lanzhou, Gansu, China; zhangyanan@impcas.ac.cn.
  • 15 Institute of Modern Physics Chinese Academy of Sciences, 71200, Lanzhou, Gansu, China; huajunrui@impcas.ac.cn.
  • 16 Institute of Modern Physics Chinese Academy of Sciences, 71200, Lanzhou, Gansu, China; jufangwang@impcas.ac.cn.
  • 17 Gansu University of Traditional Chinese Medicine, 381940, Lanzhou, Gansu, China; liuyongqi73@63.com.
PMID: 36242096 DOI: 10.1089/ars.2022.0072
Abstract

Radiation-induced bystander effects (RIBE) can cause genomic damage in bone marrow mesenchymal stem cells (BMSCs) residing in the lung Cancer microenvironment. This effect appears in the short-term as well as in the long-term and can be characterized by different levels and types of cytokines. Depending on the degree of damage, stem cells have different survival fates. Here, we describe the molecular mechanism of tumor-associated BMSC genomic instability caused by differential changes of TGF-β1 and TNF-α in RIBE after different windows of analysis in the different time point clinical setting. 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. Therefore, our results may serve as a guideline for the administration of radiation protection Adjuvant drugs at different clinical stages.

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