Proton and alpha radiation-induced mutational profiles in human cells

Ionizing radiation (IR) is known to be DNA damaging and mutagenic, however less is known about which mutational footprints result from exposures of human cells to different types of IR. We were interested in the mutagenic effects of particle radiation exposures on genomes of various human cell types, in order to gauge the genotoxic risks of space travel, and of certain types of tumor radiotherapy. To this end, we exposed cultured cell lines from the blood, breast and lung to intermittent proton and alpha particle (helium nuclei) beams at doses sufficient to affect cell survival. Whole-genome sequencing revealed that mutation rates were not overall markedly increased upon proton and alpha exposures. However, there were changes in mutation spectra and distributions, such as the increases in clustered mutations and of certain types of indels and structural variants. The spectrum of mutagenic effects of particle beams may often be cell-type and/or genetic background specific. Overall, the mutational effects of recurrent exposures to proton and alpha radiation on human cells appear subtle, however further work is warranted to understand effects of chronic, long-term exposures on various human tissues.