Functional Equivalence of Gamma- and X-Ray Irradiation for Long-Term Hematopoietic and AML Transplant Outcomes in Mice

Abstract Total-body irradiation (TBI) is routinely used for myeloablation prior to mouse hematopoietic cell transplant. Widespread transition from 137 Cs γ -irradiators to X-ray systems has raised questions about whether these modalities yield equivalent biological outcomes. Although prior studies compared γ and X-ray irradiation in healthy syngeneic transplants, their performance in reciprocal congenic models and in primary acute myeloid leukemia (AML) transplant remains unclear. Here, we systematically evaluated γ and X-ray irradiation across dose and dose-rate conditions, and tested dose equivalents in CD45.1/CD45.2 reciprocal transplants and in AML transplant models. While each modality exhibited distinct early effects, both ultimately supported comparable long-term donor chimerism in congenic transplants and equivalent AML engraftment, leukemic burden, and disease progression. These findings indicate that, with proper dose calibration, X-ray irradiation is a functionally effective alternative to γ -irradiation for normal and malignant transplant studies. Full Text Availability The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. The full text is available from the preprint server.