Unraveling cellular dynamic changes in tumor evolution induced by long-term low dose-rate radiation

Area of Science:

• Environmental Health
• Radiation Biology
• Cancer Research

Background:

• Growing number of professionals in radioactive work necessitates understanding long-term low dose-rate radiation effects.
• Biological impacts of chronic low-dose radiation exposure are not well-understood due to limited systematic research.

Purpose of the Study:

• To investigate the biological impacts of long-term low dose-rate radiation exposure on cellular malignancy.
• To elucidate the molecular mechanisms driving tumor evolution under chronic radiation exposure.

Main Methods:

• Established a BEAS-2B cell model with continuous passaging post-radiation exposure.
• Conducted in vivo tumorigenesis and in vitro malignant phenotype experiments.
• Utilized scRNA-seq, FACS, molecular docking, multiplex IHC, qRT-PCR, and co-immunoprecipitation for comprehensive analysis.

Main Results:

• Long-term low dose-rate exposure significantly increased malignancy, evidenced by copy number variations (CNV) and epithelial-mesenchymal transition (EMT) events.
• Delayed activation of DNA repair pathways led to increased genomic instability.
• Identified the ANGPTL4-SDC4 ligand-receptor pair as a key driver of angiogenesis and enhanced cell malignancy.

Conclusions:

• Provides the first mechanistic explanation for increased cellular malignancy due to long-term low dose-rate radiation.
• Offers insights into early tumor evolution dynamics in lung cancer.
• Highlights the role of specific molecular interactions in radiation-induced carcinogenesis.