Comparative Transcriptomic Analysis Unveils Divergent Effects of FLASH Versus Conventional Irradiation on Skin Cells

Area of Science:

• Radiation oncology
• Molecular biology
• Dermatology

Background:

• Conventional radiotherapy (CONV-IR) can cause significant skin toxicity.
• FLASH radiotherapy (FLASH-IR) offers potential for reduced skin toxicity without compromising anti-tumor effects.
• The molecular mechanisms underlying FLASH-IR's effects on skin remain largely unknown.

Purpose of the Study:

• To compare the transcriptomic responses of human foreskin fibroblast cells (HFF-1) to FLASH-IR and CONV-IR.
• To identify differentially expressed genes (DEGs) and molecular pathways affected by each irradiation method.
• To elucidate the molecular interplay between FLASH-IR and conventional radiotherapy in skin cells.

Main Methods:

• Utilized next-generation RNA sequencing (RNA-seq) to analyze gene expression profiles.
• Exposed HFF-1 cells to both FLASH-IR and CONV-IR.
• Performed comparative analysis of transcriptomic data and validated key DEGs using qPCR.

Main Results:

• Identified distinct sets of DEGs, signaling pathways, and transcriptional networks for FLASH-IR and CONV-IR.
• Observed significant upregulation of transcription factor NR4A1 in response to FLASH-IR.
• Found marked downregulation of chromatin stability factor ELF3 following CONV-IR, with qPCR validation of top DEGs.

Conclusions:

• FLASH-IR and CONV-IR induce unique molecular and regulatory landscapes in skin cells.
• Findings support the potential of FLASH-IR for reduced skin toxicity.
• This study provides novel molecular insights into the effects of ultra-high dose rate radiation.