Mlh1 deficiency increases the risk of hematopoietic malignancy after simulated space radiation exposure.
Animals
Biomarkers
Cell Transformation, Neoplastic
/ genetics
Disease Models, Animal
Disease Susceptibility
Environmental Exposure
/ adverse effects
Female
Hematologic Neoplasms
/ etiology
Heterozygote
Humans
INDEL Mutation
Immunohistochemistry
Incidence
Male
Mice
Mice, Knockout
Microsatellite Instability
MutL Protein Homolog 1
/ deficiency
Polymorphism, Single Nucleotide
Radiation Exposure
/ adverse effects
Risk Assessment
Risk Factors
Exome Sequencing
Journal
Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
06
07
2018
accepted:
29
08
2018
revised:
20
08
2018
pubmed:
3
10
2018
medline:
14
8
2019
entrez:
3
10
2018
Statut:
ppublish
Résumé
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
Identifiants
pubmed: 30275527
doi: 10.1038/s41375-018-0269-8
pii: 10.1038/s41375-018-0269-8
pmc: PMC6443507
mid: NIHMS1505442
doi:
Substances chimiques
Biomarkers
0
MLH1 protein, human
0
MutL Protein Homolog 1
EC 3.6.1.3
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Pagination
1135-1147Subventions
Organisme : NCI NIH HHS
ID : P30 CA043703
Pays : United States
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