Mlh1 deficiency increases the risk of hematopoietic malignancy after simulated space radiation exposure.

ABSTRACT: Cancer-causing genome instability is a major concern during space travel due to exposure of astronauts to potent sources of high-linear energy transfer (LET) ionizing radiation. Hematopoietic stem cells (HSCs) are particularly susceptible to genotoxic stress, and accumulation of damage can lead to HSC dysfunction and oncogenesis. Our group recently demonstrated that aging human HSCs accumulate microsatellite instability coincident with loss of MLH1, a DNA Mismatch Repair (MMR) protein, which could reasonably predispose to radiation-induced HSC malignancies. Therefore, in an effort to reduce risk uncertainty for cancer development during deep space travel, we employed an Mlh1^+/- mouse model to study the effects high-LET ⁵⁶Fe ion space-like radiation. Irradiated Mlh1

SUBMITTER: Patel R 

PROVIDER: S-EPMC6443507 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature