Megan A Evans, Heather Doviak, Ariel H Polizio, Jesse D Cochran, Leslie R Kim, Eunbee Park, Mark C Thel, Christopher R Xie, Ajay R Srinivasan, Lucila Marino, Yoshimitsu Yura, Hanna Sun, Sahithi Mikkilineni, Andrew J McKamy, George Philippos, Ana Filipa Domingues, George S Vassiliou, Samantha C St Jean, Eric M Pietras, David A Goukassian, Kenneth Walsh
The effects of space radiation on clonal hematopoiesis (CH) and its impact on long-term health outcomes are unknown. Using male and female murine models of Trp53-, Ppm1d-, and Tet2-mediated CH, we examined the effects of exposure to gamma radiation, simulated solar particle events, or simplified simulated galactic cosmic rays on the clonal expansion of mutant cells and long-term health outcomes. Radiation accelerated the expansion of Trp53 and Ppm1d, but not Tet2, mutant clones. Over 18 months, male mice with Trp53 mutant cells showed worse survival than controls, which was exacerbated following radiation exposure. The interaction between the mutation and radiation exposure was absent for the other driver genes and in female mice with Trp53 mutations. Male mice with Trp53 mutant cells exhibited evidence of hematologic disease and hematopoietic loss of the Y chromosome. Male astronauts with TP53 clonal hematopoiesis may be at elevated risk of clone growth and hematologic disease following radiation exposure.