Proton and alpha radiation-induced mutational profiles in human cells

Area of Science:

• Genotoxicology
• Radiation Biology
• Genomics

Background:

• Ionizing radiation is a known DNA mutagen.
• Understanding radiation-induced mutational footprints in human cells is crucial for assessing risks associated with space travel (galactic cosmic radiation) and cancer radiotherapy.
• Specific effects of particle radiation on human cell genomes require further investigation.

Purpose of the Study:

• To investigate the mutagenic effects of proton and alpha particle radiation on human blood, breast, and lung cell lines.
• To characterize the resulting mutational footprints and genotoxic risks.
• To assess the cell-type specificity of radiation-induced mutations.

Main Methods:

• Exposing cultured human cell lines (blood, breast, lung) to fractionated proton and alpha particle beams.
• Administering doses sufficient to impact cell viability.
• Performing whole-genome sequencing to analyze mutation rates, spectra, and distributions.

Main Results:

• Overall mutation rates were not significantly increased by proton and alpha particle exposures.
• Modest alterations in mutation spectra were observed, including an increase in clustered mutations.
• Specific types of insertions/deletions (indels) and structural variants showed changes.
• Mutagenic effects appeared to be cell-type and genetic background dependent.

Conclusions:

• Repeated exposure to proton and alpha radiation has subtle mutational effects on human cells in culture.
• Observed changes include increased clustered mutations and specific indels/structural variants.
• Further studies are warranted to elucidate the long-term consequences of radiation exposure on diverse human tissues.