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Proton and alpha radiation-induced mutational profiles in human cells

View ORCID ProfileTiffany M. Delhomme, Manuela Buonanno, Veljko Grilj, View ORCID ProfileJosep Biayna, View ORCID ProfileFran Supek
doi: https://doi.org/10.1101/2022.07.29.501997
Tiffany M. Delhomme
1Genome Data Science, Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain
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Manuela Buonanno
2Radiological Research Accelerator Facility (RARAF), Columbia University, New York, USA
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Veljko Grilj
2Radiological Research Accelerator Facility (RARAF), Columbia University, New York, USA
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Josep Biayna
1Genome Data Science, Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain
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Fran Supek
1Genome Data Science, Institute for Research in Biomedicine (IRB Barcelona), Barcelona, Spain
3Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain
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  • For correspondence: fran.supek@irbbarcelona.org
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Abstract

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.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted July 29, 2022.
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Proton and alpha radiation-induced mutational profiles in human cells
Tiffany M. Delhomme, Manuela Buonanno, Veljko Grilj, Josep Biayna, Fran Supek
bioRxiv 2022.07.29.501997; doi: https://doi.org/10.1101/2022.07.29.501997
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Proton and alpha radiation-induced mutational profiles in human cells
Tiffany M. Delhomme, Manuela Buonanno, Veljko Grilj, Josep Biayna, Fran Supek
bioRxiv 2022.07.29.501997; doi: https://doi.org/10.1101/2022.07.29.501997

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