title: Radiation Sensitivity of Human CD34(+) Cells Versus Peripheral Blood T Lymphocytes of Newborns and Adults: DNA Repair and Mutagenic Effects.
abstract: As hematopoietic stem and progenitor cells (HSPCs) self-renew throughout life, accumulation of genomic alterations can potentially give rise to radiation carcinogenesis. In this study we examined DNA double-strand break (DSB) induction and repair as well as mutagenic effects of ionizing radiation in CD34(+) cells and T lymphocytes from the umbilical cord of newborns. The age dependence of DNA damage repair end points was investigated by comparing newborn T lymphocytes with adult peripheral blood T lymphocytes. As umbilical cord blood (UCB) contains T lymphocytes that are practically all phenotypically immature, we examined the radiation response of separated naive (CD45RA(+)) and memory (CD45RO(+)) T lymphocytes. The number of DNA DSBs was assessed by microscopic scoring of γ-H2AX/53BP1 foci 0.5 h after low-dose radiation exposure, while DNA repair was studied by scoring the number of residual γ-H2AX/53BP1 foci 24 h after exposure. Mutagenic effects were studied by the cytokinesis block micronucleus (CBMN) assay. No significant differences in the number of DNA DSBs induced by low-dose (100-200 mGy) radiation were observed among the three different cell types. However, residual γ-H2AX/53BP1 foci levels 24 h postirradiation were significantly lower in CD34(+) cells compared to newborn T lymphocytes, while newborn T lymphocytes showed significantly higher foci yields than adult T lymphocytes. No significant differences in the level of radiation-induced micronuclei at 2 Gy were observed between CD34(+) cells and newborn T lymphocytes. However, newborn T lymphocytes showed a significantly higher number of micronuclei compared to adult T lymphocytes. These results confirm that CD34(+) cell quiescence promotes mutagenesis after exposure. Furthermore, we can conclude that newborn peripheral T lymphocytes are significantly more radiosensitive than adult peripheral T lymphocytes. Using the results from the comparative study of radiation-induced DNA damage repair end points in naive (CD45RA(+)) and memory (CD45RO(+)) T lymphocytes, we could demonstrate that the observed differences between newborn and adult T lymphocytes can be explained by the immunophenotypic change of T lymphocytes with age, which is presumably linked with the remodeling of the closed chromatin structure of naive T lymphocytes.
authors.affiliation: a   Departments of Basic Medical Sciences and.
authors.forename: C
authors.initials: C
authors.lastname: Vandevoorde
authors.affiliation: a   Departments of Basic Medical Sciences and.
authors.forename: A
authors.initials: A
authors.lastname: Vral
authors.affiliation: b   Clinical Chemistry, Microbiology and Immunology, Ghent University, Gent, Belgium.
authors.forename: B
authors.initials: B
authors.lastname: Vandekerckhove
authors.affiliation: b   Clinical Chemistry, Microbiology and Immunology, Ghent University, Gent, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Philippé
authors.affiliation: a   Departments of Basic Medical Sciences and.
authors.forename: H
authors.initials: H
authors.lastname: Thierens
mesh_terms: D000328:Adult; D000375:Aging / Q000235:genetics / Q000528:radiation effects; D018952:Antigens, CD34 / Q000378:metabolism*; D004260:DNA Repair / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007231:Infant, Newborn; D009153:Mutagens / Q000009:adverse effects*; D011836:Radiation Tolerance; D013601:T-Lymphocytes / Q000378:metabolism* / Q000528:radiation effects*; D014965:X-Rays / Q000009:adverse effects
chemical_list: D018952:Antigens, CD34; D009153:Mutagens